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Shin S, Jiang D, Yu J, Yang C, Jeong W, Li J, Bae J, Shin J, An K, Kim W, Cho NJ. Interaction Dynamics of Liposomal Fatty Acids with Gram-Positive Bacterial Membranes. ACS APPLIED MATERIALS & INTERFACES 2025; 17:23666-23679. [PMID: 40223206 DOI: 10.1021/acsami.5c00787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/15/2025]
Abstract
The increasing prevalence of antibiotic-resistant bacteria has driven the need for alternative therapeutic strategies, with liposomal fatty acids (LipoFAs) emerging as promising candidates due to their potent antibacterial properties. Despite growing interest, the detailed biophysical interactions between LipoFAs and bacterial membranes remain underexplored. In this study, we systematically investigate the mechanistic interactions of liposomal linolenic acid (LipoLNA), linoleic acid (LipoLLA), and oleic acid (LipoOA) with model Gram-positive bacterial membranes using quartz crystal microbalance with dissipation (QCM-D) and fluorescence microscopy. QCM-D analysis revealed that LipoOA displayed the highest rate of membrane fusion, followed by LipoLLA and LipoLNA. Fluorescence microscopy highlighted distinct morphological changes induced by each LipoFA: LipoLNA generated large membrane buds, LipoLLA formed smaller dense protrusions, and LipoOA caused rapid incorporation with uniform dense spots. Furthermore, fluorescence recovery after photobleaching (FRAP) demonstrated that LipoLNA significantly enhanced lipid mobility and membrane fluidity, as confirmed by Laurdan generalized polarization measurements. The extent of unsaturation in LipoFAs was found to play a critical role in their interaction mechanism, with higher degrees of unsaturation inducing greater local curvature stress, increased membrane permeability, and substantial ATP leakage, ultimately leading to improved bactericidal activity. Notably, liposomal formulations exhibited enhanced biocompatibility compared to free fatty acids. These findings provide valuable mechanistic insights into how LipoFAs perturb bacterial membranes, supporting their potential application as alternative antibacterial agents.
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Affiliation(s)
- Sungmin Shin
- School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore
- Singapore-HUJ Alliance for Research and Enterprise, Singapore HUJ Alliance Research Enterprise (SHARE) 1 CREATE Way, #03-09 Innovation Wing, Singapore 138602, Singapore
- Centre for Cross Economy, Nanyang Technological University, 60 Nanyang Drive, SBS-01s-50, Singapore 637551, Singapore
| | - Dongping Jiang
- School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore
- Singapore-HUJ Alliance for Research and Enterprise, Singapore HUJ Alliance Research Enterprise (SHARE) 1 CREATE Way, #03-09 Innovation Wing, Singapore 138602, Singapore
- Centre for Cross Economy, Nanyang Technological University, 60 Nanyang Drive, SBS-01s-50, Singapore 637551, Singapore
| | - Jingyeong Yu
- College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea
| | - Chungmo Yang
- School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore
| | - Woncheol Jeong
- School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore
- Centre for Cross Economy, Nanyang Technological University, 60 Nanyang Drive, SBS-01s-50, Singapore 637551, Singapore
| | - Jian Li
- School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore
- Centre for Cross Economy, Nanyang Technological University, 60 Nanyang Drive, SBS-01s-50, Singapore 637551, Singapore
| | - Jieun Bae
- Department of Research and Development, LUCA AICell Inc, Anyang 14055, Republic of Korea
| | - Jihoon Shin
- School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore
- Department of Research and Development, LUCA AICell Inc, Anyang 14055, Republic of Korea
| | - Kyongman An
- Department of Research and Development, LUCA AICell Inc, Anyang 14055, Republic of Korea
| | - Wooseong Kim
- College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea
| | - Nam-Joon Cho
- School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore
- Singapore-HUJ Alliance for Research and Enterprise, Singapore HUJ Alliance Research Enterprise (SHARE) 1 CREATE Way, #03-09 Innovation Wing, Singapore 138602, Singapore
- Centre for Cross Economy, Nanyang Technological University, 60 Nanyang Drive, SBS-01s-50, Singapore 637551, Singapore
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2
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Paes Dutra JA, Gonçalves Carvalho S, Soares de Oliveira A, Borges Monteiro JR, Rodrigues Pereira de Oliveira Borlot J, Tavares Luiz M, Bauab TM, Rezende Kitagawa R, Chorilli M. Microparticles and nanoparticles-based approaches to improve oral treatment of Helicobacter pylori infection. Crit Rev Microbiol 2024; 50:728-749. [PMID: 37897442 DOI: 10.1080/1040841x.2023.2274835] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 10/17/2023] [Indexed: 10/30/2023]
Abstract
Helicobacter pylori is a gram-negative, spiral-shaped, flagellated bacterium that colonizes the stomach of half the world's population. Helicobacter pylori infection causes pathologies of varying severity. Standard oral therapy fails in 15-20% since the barriers of the oral route decrease the bioavailability of antibiotics and the intrinsic factors of bacteria increase the rates of resistance. Nanoparticles and microparticles are promising strategies for drug delivery into the gastric mucosa and targeting H. pylori. The variety of building blocks creates systems with distinct colloidal, surface, and biological properties. These features improve drug-pathogen interactions, eliminate drug depletion and overuse, and enable the association of multiple actives combating H. pylori on several fronts. Nanoparticles and microparticles are successfully used to overcome the barriers of the oral route, physicochemical inconveniences, and lack of selectivity of current therapy. They have proven efficient in employing promising anti-H. pylori compounds whose limitation is oral route instability, such as some antibiotics and natural products. However, the current challenge is the applicability of these strategies in clinical practice. For this reason, strategies employing a rational design are necessary, including in the development of nano- and microsystems for the oral route.
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Affiliation(s)
| | | | | | | | | | - Marcela Tavares Luiz
- School of Pharmaceutical Science, Sao Paulo State University (UNESP), Araraquara, Brazil
| | - Tais Maria Bauab
- School of Pharmaceutical Science, Sao Paulo State University (UNESP), Araraquara, Brazil
| | | | - Marlus Chorilli
- School of Pharmaceutical Science, Sao Paulo State University (UNESP), Araraquara, Brazil
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Chitas R, Fonseca DR, Parreira P, Martins MCL. Targeted nanotherapeutics for the treatment of Helicobacter pylori infection. J Biomed Sci 2024; 31:78. [PMID: 39128983 DOI: 10.1186/s12929-024-01068-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 07/16/2024] [Indexed: 08/13/2024] Open
Abstract
Helicobacter pylori infection is involved in gastric diseases such as peptic ulcer and adenocarcinoma. Approved antibiotherapies still fail in 10 to 40% of the infected patients and, in this scenario, targeted nanotherapeutics emerged as powerful allies for H. pylori eradication. Nano/microparticles conjugated with H. pylori binding molecules were developed to eliminate H. pylori by either (i) blocking essential mechanisms of infection, such as adhesion to gastric mucosa or (ii) binding and killing H. pylori through the release of drugs within the bacteria or at the site of infection. Glycan antigens (as Lewis B and sialyl-Lewis X), pectins, lectins, phosphatidylethanolamine and epithelial cell membranes were conjugated with nano/microparticles to successfully block H. pylori adhesion. Urea-coated nanoparticles were used to improve drug delivery inside bacteria through H. pylori UreI channel. Moreover, nanoparticles coated with antibodies against H. pylori and loaded with sono/photosensitizers, were promising for their application as targeted sono/photodynamic therapies. Further, non-specific H. pylori nano/microparticles, but only active in the acidic gastric environment, coated with binders to bacterial membrane, extracellular polymeric substances or to high temperature requirement A protease, were evaluated. In this review, an overview of the existing nanotherapeutics targeting H. pylori will be given and their rational, potential to counteract infection, as well as level of development will be presented and discussed.
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Affiliation(s)
- Rute Chitas
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal
- ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
| | - Diana R Fonseca
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal
- FEUP - Faculdade de Engenharia, Departamento de Engenharia Metalúrgica e de Materiais, Universidade do Porto, Porto, Portugal
| | - Paula Parreira
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal
| | - M Cristina L Martins
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
- INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal.
- ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
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Garg A, Karhana S, Khan MA. Nanomedicine for the eradication of Helicobacter pylori: recent advances, challenges and future perspective. Future Microbiol 2024; 19:431-447. [PMID: 38381027 DOI: 10.2217/fmb-2023-0189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Accepted: 10/31/2023] [Indexed: 02/22/2024] Open
Abstract
Helicobacter pylori infection is linked to gastritis, ulcers and gastric cancer. Nanomedicine offers a promising solution by utilizing nanoparticles for precise drug delivery, countering antibiotic resistance and delivery issues. Nanocarriers such as liposomes and nanoparticles enhance drug stability and circulation, targeting infection sites through gastric mucosa characteristics. Challenges include biocompatibility, stability, scalability and personalized therapies. Despite obstacles, nanomedicine's potential for reshaping H. pylori eradication is significant and showcased in this review focusing on benefits, limitations and future prospects of nanomedicine-based strategies.
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Affiliation(s)
- Aakriti Garg
- Department of Pharmacology, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, 110062, India
- Centre for Translational & Clinical Research, School of Chemical & Life Sciences, Jamia Hamdard, New Delhi, 110062, India
| | - Sonali Karhana
- Centre for Translational & Clinical Research, School of Chemical & Life Sciences, Jamia Hamdard, New Delhi, 110062, India
| | - Mohd A Khan
- Centre for Translational & Clinical Research, School of Chemical & Life Sciences, Jamia Hamdard, New Delhi, 110062, India
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Liu T, Chai S, Li M, Chen X, Xie Y, Zhao Z, Xie J, Yu Y, Gao F, Zhu F, Yang L. A nanoparticle-based sonodynamic therapy reduces Helicobacter pylori infection in mouse without disrupting gut microbiota. Nat Commun 2024; 15:844. [PMID: 38286999 PMCID: PMC10825188 DOI: 10.1038/s41467-024-45156-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 01/15/2024] [Indexed: 01/31/2024] Open
Abstract
Infection by Helicobacter pylori, a prevalent global pathogen, currently requires antibiotic-based treatments, which often lead to antimicrobial resistance and gut microbiota dysbiosis. Here, we develop a non-antibiotic approach using sonodynamic therapy mediated by a lecithin bilayer-coated poly(lactic-co-glycolic) nanoparticle preloaded with verteporfin, Ver-PLGA@Lecithin, in conjunction with localized ultrasound exposure of a dosage permissible for ultrasound medical devices. This study reveals dual functionality of Ver-PLGA@Lecithin. It effectively neutralizes vacuolating cytotoxin A, a key virulence factor secreted by H. pylori, even in the absence of ultrasound. When coupled with ultrasound exposure, it inactivates H. pylori by generating reactive oxygen species, offering a potential solution to overcome antimicrobial resistance. In female mouse models bearing H. pylori infection, this sonodynamic therapy performs comparably to the standard triple therapy in reducing gastric infection. Significantly, unlike the antibiotic treatments, the sonodynamic therapy does not negatively disrupt gut microbiota, with the only major impact being upregulation of Lactobacillus, which is a bacterium widely used in yogurt products and probiotics. This study presents a promising alternative to the current antibiotic-based therapies for H. pylori infection, offering a reduced risk of antimicrobial resistance and minimal disturbance to the gut microbiota.
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Affiliation(s)
- Tao Liu
- Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, China
- CAS Key Laboratory of Soft Matter Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, China
- School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Shuang Chai
- Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, China
- CAS Key Laboratory of Soft Matter Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, China
- School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Mingyang Li
- Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, China
- CAS Key Laboratory of Soft Matter Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, China
- School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Xu Chen
- Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, China
- CAS Key Laboratory of Soft Matter Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, China
- School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Yutao Xie
- Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, China
- CAS Key Laboratory of Soft Matter Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, China
- School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Zehui Zhao
- Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, China
- CAS Key Laboratory of Soft Matter Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, China
- School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Jingjing Xie
- Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, China
- CAS Key Laboratory of Soft Matter Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, China
- School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Yunpeng Yu
- Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, China
- CAS Key Laboratory of Soft Matter Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, China
- School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Feng Gao
- Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Feng Zhu
- Division of Life Science and Medicine, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Lihua Yang
- Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, China.
- CAS Key Laboratory of Soft Matter Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, China.
- School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui, 230026, China.
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Meng Y, Chen S, Wang C, Ni X. Advances in Composite Biofilm Biomimetic Nanodrug Delivery Systems for Cancer Treatment. Technol Cancer Res Treat 2024; 23:15330338241250244. [PMID: 38693842 PMCID: PMC11067686 DOI: 10.1177/15330338241250244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Revised: 02/27/2024] [Accepted: 04/08/2024] [Indexed: 05/03/2024] Open
Abstract
Single biofilm biomimetic nanodrug delivery systems based on single cell membranes, such as erythrocytes and cancer cells, have immune evasion ability, good biocompatibility, prolonged blood circulation, and high tumor targeting. Because of the different characteristics and functions of each single cell membrane, more researchers are using various hybrid cell membranes according to their specific needs. This review focuses on several different types of biomimetic nanodrug-delivery systems based on composite biofilms and looks forward to the challenges and possible development directions of biomimetic nanodrug-delivery systems based on composite biofilms to provide reference and ideas for future research.
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Affiliation(s)
- Yanyan Meng
- School of Pharmacy, Changzhou University, Changzhou, China
- Department of Radiotherapy Oncology, the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China
- Medical Physics Research Center, Nanjing Medical University, Changzhou, China
- Changzhou Key Laboratory of Medical Physics, Changzhou, China
| | - Shaoqing Chen
- Department of Radiotherapy Oncology, the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China
- Medical Physics Research Center, Nanjing Medical University, Changzhou, China
- Changzhou Key Laboratory of Medical Physics, Changzhou, China
| | - Cheli Wang
- School of Pharmacy, Changzhou University, Changzhou, China
| | - Xinye Ni
- Department of Radiotherapy Oncology, the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China
- Medical Physics Research Center, Nanjing Medical University, Changzhou, China
- Changzhou Key Laboratory of Medical Physics, Changzhou, China
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Cheng X, Geng J, Wang L, Ma X, Su Y, Arif M, Liu C. Berberine-loaded mannosylerythritol lipid-B nanomicelles as drug delivery carriers for the treatment of Helicobacter pylori biofilms in vivo. Eur J Pharm Biopharm 2023; 193:S0939-6411(23)00287-4. [PMID: 39492446 DOI: 10.1016/j.ejpb.2023.10.021] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 10/21/2023] [Accepted: 10/27/2023] [Indexed: 11/05/2024]
Abstract
Eradication of Helicobacter pylori biofilm is crucial to the treatment of H. pylori infections, especially regarding the challenge of fast development of antibiotic resistance in H. pylori worldwide. Herein, a self-assembled berberine-loaded MEL-B nanomicelle (MEL-B NMs/BBR4) gastric delivery carrier was established to combat biofilm-induced H. pylori resistance in vivo. MEL-B NMs/BBR4 were tolerant to the stomach's acidic environment for the first 2 h and could quickly penetrate the mucus layer to reach the H. pylori colonization site. In addition, MEL-B NMs/BBR4 could damage the architecture of H. pylori biofilms, and simultaneously kill dispersed H. pylori cells by berberine and inhibit the formation of H. pylori biofilms. Significantly, MEL-B NMs/BBR4 decreased the H. pylori burden by 2 orders of magnitude and repaired the damaged gastric mucosal barrier while reducing the inflammatory response in vivo. In brief, this study provides a new strategy for using a fully natural nanodrug to effectively eradicate H. pylori biofilms in vivo.
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Affiliation(s)
- Xiaohong Cheng
- College of Marine Life Sciences, Ocean University of China, No.5 Yushan Road, 266003, Qingdao, China
| | - Jiayue Geng
- College of Marine Life Sciences, Ocean University of China, No.5 Yushan Road, 266003, Qingdao, China
| | - Lili Wang
- Central Laboratories, Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Xishuai Ma
- College of Marine Life Sciences, Ocean University of China, No.5 Yushan Road, 266003, Qingdao, China
| | - Yun Su
- College of Marine Life Sciences, Ocean University of China, No.5 Yushan Road, 266003, Qingdao, China
| | - Muhammad Arif
- College of Marine Life Sciences, Ocean University of China, No.5 Yushan Road, 266003, Qingdao, China
| | - Chenguang Liu
- College of Marine Life Sciences, Ocean University of China, No.5 Yushan Road, 266003, Qingdao, China.
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Almanza-Aguilera E, Cano A, Gil-Lespinard M, Burguera N, Zamora-Ros R, Agudo A, Farràs M. Mediterranean diet and olive oil, microbiota, and obesity-related cancers. From mechanisms to prevention. Semin Cancer Biol 2023; 95:103-119. [PMID: 37543179 DOI: 10.1016/j.semcancer.2023.08.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 07/02/2023] [Accepted: 08/01/2023] [Indexed: 08/07/2023]
Abstract
Olive oil (OO) is the main source of added fat in the Mediterranean diet (MD). It is a mix of bioactive compounds, including monounsaturated fatty acids, phytosterols, simple phenols, secoiridoids, flavonoids, and terpenoids. There is a growing body of evidence that MD and OO improve obesity-related factors. In addition, obesity has been associated with an increased risk for several cancers: endometrial, oesophageal adenocarcinoma, renal, pancreatic, hepatocellular, gastric cardia, meningioma, multiple myeloma, colorectal, postmenopausal breast, ovarian, gallbladder, and thyroid cancer. However, the epidemiological evidence linking MD and OO with these obesity-related cancers, and their potential mechanisms of action, especially those involving the gut microbiota, are not clearly described or understood. The goals of this review are 1) to update the current epidemiological knowledge on the associations between MD and OO consumption and obesity-related cancers, 2) to identify the gut microbiota mechanisms involved in obesity-related cancers, and 3) to report the effects of MD and OO on these mechanisms.
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Affiliation(s)
- Enrique Almanza-Aguilera
- Unit of Nutrition and Cancer, Epidemiology Research Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Spain
| | - Ainara Cano
- Food Research, AZTI, Basque Research and Technology Alliance (BRTA), Parque Tecnológico de Bizkaia, Astondo Bidea, Edificio 609, 48160, Derio, Spain
| | - Mercedes Gil-Lespinard
- Unit of Nutrition and Cancer, Epidemiology Research Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Spain
| | - Nerea Burguera
- Food Research, AZTI, Basque Research and Technology Alliance (BRTA), Parque Tecnológico de Bizkaia, Astondo Bidea, Edificio 609, 48160, Derio, Spain
| | - Raul Zamora-Ros
- Unit of Nutrition and Cancer, Epidemiology Research Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Spain; Department of Nutrition, Food Sciences, and Gastronomy, Food Innovation Network (XIA), Institute for Research on Nutrition and Food Safety (INSA), Faculty of Pharmacy and Food Sciences University of Barcelona, Barcelona, Spain.
| | - Antonio Agudo
- Unit of Nutrition and Cancer, Epidemiology Research Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Spain
| | - Marta Farràs
- Unit of Nutrition and Cancer, Epidemiology Research Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Spain.
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Cheng W, He L, Ren W, Yue T, Xie X, Sun J, Chen X, Wu Z, Li F, Piao JG. Bacteria-nanodrug cancer treatment system: The combination of dual swords and the confrontation of needle tips. NANO TRANSMED 2023; 2:100008. [DOI: 10.1016/j.ntm.2023.100008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/11/2023]
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10
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Cheng W, He L, Ren W, Yue T, Xie X, Sun J, Chen X, Wu Z, Li F, Piao JG. Bacteria-nanodrug cancer treatment system: The combination of dual swords and the confrontation of needle tips. NANO TRANSMED 2023; 2:100008. [DOI: 10.1016/j.ntm.2023.100008 received in revised form 24 august 2023; acce] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/11/2023]
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11
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Zhou WT, Dai YY, Liao LJ, Yang SX, Chen H, Huang L, Zhao JL, Huang YQ. Linolenic acid-metronidazole inhibits the growth of Helicobacter pylori through oxidation. World J Gastroenterol 2023; 29:4860-4872. [PMID: 37701137 PMCID: PMC10494766 DOI: 10.3748/wjg.v29.i32.4860] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 07/15/2023] [Accepted: 07/31/2023] [Indexed: 08/25/2023] Open
Abstract
BACKGROUND Resistance to antibiotics is one the main factors constraining the treatment and control of Helicobacter pylori (H. pylori) infections. Therefore, there is an urgent need to develop new antimicrobial agents to replace antibiotics. Our previous study found that linolenic acid-metronidazole (Lla-Met) has a good antibacterial effect against H. pylori, both antibiotic-resistant and sensitive H. pylori. Also, H. pylori does not develop resistance to Lla-Met. Therefore, it could be used for preparing broad-spectrum antibacterial agents. However, since the antibacterial mechanism of Lla-Met is not well understood, we explored this phenomenon in the present study. AIM To understand the antimicrobial effect of Lla-Met and how this could be applied in treating corresponding infections. METHODS H. pylori cells were treated with the Lla-Met compound, and the effect of the compound on the cell morphology, cell membrane permeability, and oxidation of the bacteria cell was assessed. Meanwhile, the differently expressed genes in H. pylori in response to Lla-Met treatment were identified. RESULTS Lla-Met treatment induced several changes in H. pylori cells, including roughening and swelling. In vivo experiments revealed that Lla-Met induced oxidation, DNA fragmentation, and phosphatidylserine ectropionation in H. pylori cells. Inhibiting Lla-Met with L-cysteine abrogated the above phenomena. Transcriptome analysis revealed that Lla-Met treatment up-regulated the expression of superoxide dismutase SodB and MdaB genes, both anti-oxidation-related genes. CONCLUSION Lla-Met kills H. pylori mainly by inducing oxidative stress, DNA damage, phosphatidylserine ectropionation, and changes on cell morphology.
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Affiliation(s)
- Wen-Ting Zhou
- School of Basic Medicine, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Yuan-Yuan Dai
- School of Basic Medicine, Youjiang Medical University for Nationalities, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Li-Juan Liao
- School of Basic Medicine, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Shi-Xian Yang
- Department of Laboratory, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Hao Chen
- School of Basic Medicine, Department of Pathology, Wannan Medical College, Wuhu 533000, Anhui Province, China
| | - Liang Huang
- School of Basic Medicine, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
- Key Laboratory of the Prevention and Treatment of Drug Resistant Microbial Infecting, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Juan-Li Zhao
- School of Basic Medicine, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Yan-Qiang Huang
- School of Basic Sciences, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
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12
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Liu Y, Niu L, Li N, Wang Y, Liu M, Su X, Bao X, Yin B, Shen S. Bacterial-Mediated Tumor Therapy: Old Treatment in a New Context. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2205641. [PMID: 36908053 PMCID: PMC10131876 DOI: 10.1002/advs.202205641] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 02/09/2023] [Indexed: 06/18/2023]
Abstract
Targeted therapy and immunotherapy have brought hopes for precision cancer treatment. However, complex physiological barriers and tumor immunosuppression result in poor efficacy, side effects, and resistance to antitumor therapies. Bacteria-mediated antitumor therapy provides new options to address these challenges. Thanks to their special characteristics, bacteria have excellent ability to destroy tumor cells from the inside and induce innate and adaptive antitumor immune responses. Furthermore, bacterial components, including bacterial vesicles, spores, toxins, metabolites, and other active substances, similarly inherit their unique targeting properties and antitumor capabilities. Bacteria and their accessory products can even be reprogrammed to produce and deliver antitumor agents according to clinical needs. This review first discusses the role of different bacteria in the development of tumorigenesis and the latest advances in bacteria-based delivery platforms and the existing obstacles for application. Moreover, the prospect and challenges of clinical transformation of engineered bacteria are also summarized.
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Affiliation(s)
- Yao Liu
- Key Laboratory of Spine and Spinal Cord Injury Repairand Regeneration of Ministry of EducationOrthopaedic Department of Tongji Hospital, The Institute for Biomedical Engineering and Nano ScienceTongji University School of MedicineShanghai200092P. R. China
- Pharmacy Department and Center for Medical Research and InnovationShanghai Pudong HospitalFudan University Pudong Medical CenterShanghai201399China
| | - Lili Niu
- Central LaboratoryFirst Affiliated HospitalInstitute (College) of Integrative MedicineDalian Medical UniversityDalian116021China
| | - Nannan Li
- Central LaboratoryFirst Affiliated HospitalInstitute (College) of Integrative MedicineDalian Medical UniversityDalian116021China
| | - Yang Wang
- Central LaboratoryFirst Affiliated HospitalInstitute (College) of Integrative MedicineDalian Medical UniversityDalian116021China
| | - Mingyang Liu
- Department of Surgical Oncology and General SurgeryThe First Hospital of China Medical University155 North Nanjing Street, Heping DistrictShenyang110001China
| | - Xiaomin Su
- Central LaboratoryFirst Affiliated HospitalInstitute (College) of Integrative MedicineDalian Medical UniversityDalian116021China
| | - Xuhui Bao
- Institute for Therapeutic Cancer VaccinesFudan University Pudong Medical CenterShanghai201399China
| | - Bo Yin
- Institute for Therapeutic Cancer Vaccines and Department of OncologyFudan University Pudong Medical CenterShanghai201399China
| | - Shun Shen
- Pharmacy Department and Center for Medical Research and InnovationShanghai Pudong HospitalFudan University Pudong Medical CenterShanghai201399China
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13
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Fan L, Wei A, Gao Z, Mu X. Current progress of mesenchymal stem cell membrane-camouflaged nanoparticles for targeted therapy. Biomed Pharmacother 2023; 161:114451. [PMID: 36870279 DOI: 10.1016/j.biopha.2023.114451] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 02/17/2023] [Accepted: 02/26/2023] [Indexed: 03/06/2023] Open
Abstract
Nanodrug delivery systems have been widely used in disease treatment. However, weak drug targeting, easy to be cleared by the immune system, and low biocompatibility are great obstacles for drug delivery. As an important part of cell information transmission and behavior regulation, cell membrane can be used as drug coating material which represents a promising strategy and can overcome these limitations. Mesenchymal stem cell (MSC) membrane, as a new carrier, has the characteristics of active targeting and immune escape of MSC, and has broad application potential in tumor treatment, inflammatory disease, tissue regeneration and other fields. Here, we review recent progress on the use of MSC membrane-coated nanoparticles for therapy and drug delivery, aiming to provide guidance for the design and clinical application of membrane carrier in the future.
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Affiliation(s)
- Lianlian Fan
- Department of Pharmacy, China-Japan Union Hospital, Jilin University, Changchun130033, China
| | - Anhui Wei
- Department of Regenerative Medicine, College of Pharmacy, Jilin University, Changchun130021, China
| | - Zihui Gao
- Changchun City Experimental High School, Changchun130117, China
| | - Xupeng Mu
- Scientific Research Center, China-Japan Union Hospital, Jilin University, Changchun130033, China.
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14
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Wu J, Zhang B, Lin N, Gao J. Recent nanotechnology-based strategies for interfering with the life cycle of bacterial biofilms. Biomater Sci 2023; 11:1648-1664. [PMID: 36723075 DOI: 10.1039/d2bm01783k] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Biofilm formation plays an important role in the resistance development in bacteria to conventional antibiotics. Different properties of the bacterial strains within biofilms compared with their planktonic states and the protective effect of extracellular polymeric substances contribute to the insusceptibility of bacterial cells to conventional antimicrobials. Although great effort has been devoted to developing novel antibiotics or synthetic antibacterial compounds, their efficiency is overshadowed by the growth of drug resistance. Developments in nanotechnology have brought various feasible strategies to combat biofilms by interfering with the biofilm life cycle. In this review, recent nanotechnology-based strategies for interfering with the biofilm life cycle according to the requirements of different stages are summarized. Additionally, the importance of strategies that modulate the bacterial biofilm microenvironment is also illustrated with specific examples. Lastly, we discussed the remaining challenges and future perspectives on nanotechnology-based strategies for the treatment of bacterial infection.
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Affiliation(s)
- Jiahe Wu
- Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China. .,Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
| | - Bo Zhang
- Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.
| | - Nengming Lin
- Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.
| | - Jianqing Gao
- Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
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15
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Qu S, Han Y, Liu Y, Zhu J, Acaroz U, Shen J, Zhu K. Milk Exosomes Facilitate Oral Delivery of Drugs against Intestinal Bacterial Infections. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:16069-16079. [PMID: 36515136 DOI: 10.1021/acs.jafc.2c04971] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
Biopharmaceutics Classification System (BCS) class II and IV drugs exhibit low solubility and suffer a limitation in oral administration. Exosomes have attracted intensive attention in the efficient delivery of such compounds. However, low gastrointestinal stability and high production cost of exosomes hinder their development as drug carriers. Here, milk exosomes are functionalized with phosphatidylserine and are capable of improving the solubility of BCS class II and IV drugs, resulting in facilitating the oral delivery of the drugs. A natural flavonoid, α-mangostin, is loaded into exosomes (AExo) to enhance the antibacterial efficiency, demonstrated by clearing 99% of bacteria in macrophages. Furthermore, AExo exhibits high mucus penetrability and shows a significant therapeutic efficacy in two animal infection models. Collectively, this work expands the application of exosomes from bovine milk with simple operation and low cost, shedding light on the potential of milk exosomes in improving the solubility of drugs to enhance the efficacy of oral administration.
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Affiliation(s)
- Shaoqi Qu
- Key Laboratory of Traditional Chinese Veterinary Medicine Biology, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China
| | - Yiming Han
- College of Engineering, Peking University, Beijing 100871, China
| | - Ying Liu
- Key Laboratory of Traditional Chinese Veterinary Medicine Biology, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
| | - Jiajia Zhu
- Key Laboratory of Traditional Chinese Veterinary Medicine Biology, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
| | - Ulas Acaroz
- Department of Food Hygiene and Technology, Faculty of Veterinary Medicine, Afyon Kocatepe University, Afyonkarahisar 03200, Turkey
| | - Jianzhong Shen
- Key Laboratory of Traditional Chinese Veterinary Medicine Biology, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China
| | - Kui Zhu
- Key Laboratory of Traditional Chinese Veterinary Medicine Biology, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China
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16
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Ren R, Lim C, Li S, Wang Y, Song J, Lin TW, Muir BW, Hsu HY, Shen HH. Recent Advances in the Development of Lipid-, Metal-, Carbon-, and Polymer-Based Nanomaterials for Antibacterial Applications. NANOMATERIALS (BASEL, SWITZERLAND) 2022; 12:3855. [PMID: 36364631 PMCID: PMC9658259 DOI: 10.3390/nano12213855] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 10/28/2022] [Accepted: 10/28/2022] [Indexed: 05/29/2023]
Abstract
Infections caused by multidrug-resistant (MDR) bacteria are becoming a serious threat to public health worldwide. With an ever-reducing pipeline of last-resort drugs further complicating the current dire situation arising due to antibiotic resistance, there has never been a greater urgency to attempt to discover potential new antibiotics. The use of nanotechnology, encompassing a broad range of organic and inorganic nanomaterials, offers promising solutions. Organic nanomaterials, including lipid-, polymer-, and carbon-based nanomaterials, have inherent antibacterial activity or can act as nanocarriers in delivering antibacterial agents. Nanocarriers, owing to the protection and enhanced bioavailability of the encapsulated drugs, have the ability to enable an increased concentration of a drug to be delivered to an infected site and reduce the associated toxicity elsewhere. On the other hand, inorganic metal-based nanomaterials exhibit multivalent antibacterial mechanisms that combat MDR bacteria effectively and reduce the occurrence of bacterial resistance. These nanomaterials have great potential for the prevention and treatment of MDR bacterial infection. Recent advances in the field of nanotechnology are enabling researchers to utilize nanomaterial building blocks in intriguing ways to create multi-functional nanocomposite materials. These nanocomposite materials, formed by lipid-, polymer-, carbon-, and metal-based nanomaterial building blocks, have opened a new avenue for researchers due to the unprecedented physiochemical properties and enhanced antibacterial activities being observed when compared to their mono-constituent parts. This review covers the latest advances of nanotechnologies used in the design and development of nano- and nanocomposite materials to fight MDR bacteria with different purposes. Our aim is to discuss and summarize these recently established nanomaterials and the respective nanocomposites, their current application, and challenges for use in applications treating MDR bacteria. In addition, we discuss the prospects for antimicrobial nanomaterials and look forward to further develop these materials, emphasizing their potential for clinical translation.
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Affiliation(s)
- Ruohua Ren
- Department of Materials Science and Engineering, Faculty of Engineering, Monash University, Clayton, VIC 3800, Australia
| | - Chiaxin Lim
- Department of Materials Science and Engineering, Faculty of Engineering, Monash University, Clayton, VIC 3800, Australia
- Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia
| | - Shiqi Li
- Department of Materials Science and Engineering, Faculty of Engineering, Monash University, Clayton, VIC 3800, Australia
| | - Yajun Wang
- College of Chemistry & Materials Engineering, Wenzhou University, Wenzhou 325035, China
| | - Jiangning Song
- Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia
| | - Tsung-Wu Lin
- Department of Chemistry, Tunghai University, No.1727, Sec.4, Taiwan Boulevard, Xitun District, Taichung 40704, Taiwan
| | | | - Hsien-Yi Hsu
- School of Energy and Environment, Department of Materials Science and Engineering, City University of Hong Kong, Kowloon Tong, Hong Kong 518057, China
| | - Hsin-Hui Shen
- Department of Materials Science and Engineering, Faculty of Engineering, Monash University, Clayton, VIC 3800, Australia
- Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia
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17
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Qaiser A, Kiani MH, Parveen R, Sarfraz M, Shahnaz G, Rahdar A, Taboada P. Design and synthesis of multifunctional polymeric micelles for targeted delivery in Helicobacter pylori infection. J Mol Liq 2022. [DOI: 10.1016/j.molliq.2022.119802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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18
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Lai Y, Wei W, Du Y, Gao J, Li Z. Biomaterials for Helicobacter pylori therapy: therapeutic potential and future perspectives. Gut Microbes 2022; 14:2120747. [PMID: 36070564 PMCID: PMC9467593 DOI: 10.1080/19490976.2022.2120747] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Helicobacter pylori (H. pylori) is the main cause of gastric adenocarcinoma. However, the traditional antibiotic treatment of H. pylori is limited due to increased antibiotic resistance and low efficacy; low drug delivery efficiency and difficulties in eradicating H. pylori that is present intracellularly or in biofilms cause further setbacks. Biomaterials that can protect drugs against stomach acid, target lesions, control drug release, destroy biofilms, and exhibit unique antibacterial mechanisms and excellent biocompatibility have emerged as attractive tools for H. pylori eradication, particularly for drug-resistant strains. Herein, we review the virulence mechanisms, current drug treatments, and antibiotic resistance of H. pylori strains. Furthermore, recent advances in the development of biomaterials, including nanoparticles (such as lipid-based nanoparticles, polymeric nanoparticles, and inorganic nanoparticles), microspheres, and hydrogels, for effective and precise therapy of H. pylori and different types of therapeutic mechanisms, as well as future perspectives, have also been summarized.
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Affiliation(s)
- Yongkang Lai
- Department of Gastroenterology, Shanghai Changhai Hospital, Naval Medical University, Shanghai, China,Department of Gastroenterology, Ganzhou People’s Hospital Affiliated to Nanchang University, Ganzhou, China
| | - Wei Wei
- Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, China
| | - Yiqi Du
- Department of Gastroenterology, Shanghai Changhai Hospital, Naval Medical University, Shanghai, China
| | - Jie Gao
- Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, China,Jie Gao Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, China
| | - Zhaoshen Li
- Department of Gastroenterology, Shanghai Changhai Hospital, Naval Medical University, Shanghai, China,CONTACT Zhaoshen Li Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, 200433, China
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19
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Wu Y, Geng J, Cheng X, Yang Y, Yu Y, Wang L, Dong Q, Chi Z, Liu C. Cosmetic-Derived Mannosylerythritol Lipid-B-Phospholipid Nanoliposome: An Acid-Stabilized Carrier for Efficient Gastromucosal Delivery of Amoxicillin for In Vivo Treatment of Helicobacter pylori. ACS OMEGA 2022; 7:29086-29099. [PMID: 36033659 PMCID: PMC9404470 DOI: 10.1021/acsomega.2c02953] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 08/03/2022] [Indexed: 05/26/2023]
Abstract
Helicobacter pylori infection is a leading cause of gastritis and peptic ulcer. Current treatments for H. pylori are limited by the increase in antibiotic-resistant strains and low drug delivery to the infection site, indicating the need for effective delivery systems of antibiotics. Although liposomes are the most successful drug delivery carriers that have already been applied commercially, their acidic stability still stands as a problem. Herein, we developed a novel nanoliposome using cosmetic raw materials of mannosylerythritol lipid-B (MEL-B), soy bean lecithin, and cholesterol, namely, LipoSC-MELB. LipoSC-MELB exhibited enhanced stability under the simulated gastric-acid condition, owing to its strong intermolecular hydrogen-bond interactions caused by the incorporation of MEL-B. Moreover, amoxicillin-loaded LipoSC-MELB (LipoSC-MELB/AMX) had a particle size of approximately 100 nm and exhibited sustained drug release under varying pH conditions (pH 3-7). Besides, LipoSC-MELB/AMX exhibited significantly higher anti-H. pylori and anti-H. pylori biofilm activity as compared with free AMX. Furthermore, LipoSC-MELB was able to carry AMX across the barriers of gastric mucus and H. pylori biofilms. Remarkably, in vivo assays indicated that LipoSC-MELB/AMX was effective in treating H. pylori infection and its associated gastritis and gastric ulcers. Overall, the findings of this study showed that LipoSC-MELB was effective for gastromucosal delivery of amoxicillin to improve its bioavailability for the treatment of H. pylori infection.
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Affiliation(s)
- Yanping Wu
- College
of Marine Life Sciences, Ocean University
of China, No.5 Yushan Road, Qingdao 266003, China
| | - Jiayue Geng
- College
of Marine Life Sciences, Ocean University
of China, No.5 Yushan Road, Qingdao 266003, China
| | - Xiaohong Cheng
- College
of Marine Life Sciences, Ocean University
of China, No.5 Yushan Road, Qingdao 266003, China
| | - Ying Yang
- College
of Marine Life Sciences, Ocean University
of China, No.5 Yushan Road, Qingdao 266003, China
- Qingdao
Youdo Bioengineering Co. Ltd., No. 175 Zhuzhou Road, Qingdao 266101, China
| | - Yu Yu
- College
of Marine Life Sciences, Ocean University
of China, No.5 Yushan Road, Qingdao 266003, China
- Qingdao
Youdo Bioengineering Co. Ltd., No. 175 Zhuzhou Road, Qingdao 266101, China
| | - Lili Wang
- Central
Laboratory and Department of Gastroenterology, Qingdao Municipal Hospital, No.5 Donghai Middle Road, Qingdao 266071, China
| | - Quanjiang Dong
- Central
Laboratory and Department of Gastroenterology, Qingdao Municipal Hospital, No.5 Donghai Middle Road, Qingdao 266071, China
| | - Zhe Chi
- College
of Marine Life Sciences, Ocean University
of China, No.5 Yushan Road, Qingdao 266003, China
| | - Chenguang Liu
- College
of Marine Life Sciences, Ocean University
of China, No.5 Yushan Road, Qingdao 266003, China
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20
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Pop R, Tăbăran AF, Ungur AP, Negoescu A, Cătoi C. Helicobacter Pylori-Induced Gastric Infections: From Pathogenesis to Novel Therapeutic Approaches Using Silver Nanoparticles. Pharmaceutics 2022; 14:pharmaceutics14071463. [PMID: 35890358 PMCID: PMC9318142 DOI: 10.3390/pharmaceutics14071463] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 06/29/2022] [Accepted: 07/11/2022] [Indexed: 02/01/2023] Open
Abstract
Helicobacter pylori is the first formally recognized bacterial carcinogen and the most important single digestive pathogen responsible for the induction of gastroduodenal diseases such as gastritis, peptic ulcer, and, finally, gastric neoplasia. The recently reported high rates of antimicrobial drug resistance hamper the current therapies of H. pylori, with therapeutic failure reaching up to 40% of patients. In this context, new treatment options and strategies are urgently needed, but the successful development of these new therapeutic tools is conditioned by the understanding of the high adaptability of H. pylori to the gastric acidic environment and the complex pathogenic mechanism. Due to several advantages, including good antibacterial efficiency, possible targeted delivery, and long tissular persistence, silver nanoparticles (AgNPs) offer the opportunity of exploring new strategies to improve the H. pylori therapy. A new paradigm in the therapy of H. pylori gastric infections using AgNPs has the potential to overcome the current medical limitations imposed by the H. pylori drug resistance, which is reported for most of the current organic antibiotics employed in the classical therapies. This manuscript provides an extensive overview of the pathology of H. pylori-induced gastritis, gastric cancer, and extradigestive diseases and highlights the possible benefits and limitations of employing AgNPs in the therapeutic strategies against H. pylori infections.
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21
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Genomically Silent Refractory Gastric Cancer in a Young Patient Exhibits Overexpression of CXCL5. Curr Oncol 2022; 29:4725-4733. [PMID: 35877235 PMCID: PMC9320515 DOI: 10.3390/curroncol29070375] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 07/02/2022] [Accepted: 07/05/2022] [Indexed: 12/16/2022] Open
Abstract
Gastric cancer is the third leading cause of cancer-related deaths, with more than one million new cases and approximately 841,000 deaths annually worldwide. We report a case of a young patient (25 years old) with an aggressive form of gastric cancer. The patient had previously been treated for Helicobacter pylori (H. pylori), which is a main risk factor for developing gastric cancer. Genetic testing showed an E-cadherin (CDH1) germline mutation of unknown significance. After eight cycles of chemotherapy, a positron emission tomography (PET) scan showed disease progression with an enlarging hypermetabolic right adnexal mass suspicious for metastatic disease. Tumor pathology demonstrated invasive and poorly differentiated gastric carcinoma. The analysis of the tumor biopsy indicated the very high expression of a chemokine, C-X-C motif chemokine 5 (CXCL5). The combination of H. pylori infection with an existence of a rare CDH1 mutation could have contributed to this aggressive gastric cancer.
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22
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Wei Y, Wang J, Wu S, Zhou R, Zhang K, Zhang Z, Liu J, Qin S, Shi J. Nanomaterial-Based Zinc Ion Interference Therapy to Combat Bacterial Infections. Front Immunol 2022; 13:899992. [PMID: 35844505 PMCID: PMC9279624 DOI: 10.3389/fimmu.2022.899992] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Accepted: 05/27/2022] [Indexed: 01/04/2023] Open
Abstract
Pathogenic bacterial infections are the second highest cause of death worldwide and bring severe challenges to public healthcare. Antibiotic resistance makes it urgent to explore new antibacterial therapy. As an essential metal element in both humans and bacteria, zinc ions have various physiological and biochemical functions. They can stabilize the folded conformation of metalloproteins and participate in critical biochemical reactions, including DNA replication, transcription, translation, and signal transduction. Therefore, zinc deficiency would impair bacterial activity and inhibit the growth of bacteria. Interestingly, excess zinc ions also could cause oxidative stress to damage DNA, proteins, and lipids by inhibiting the function of respiratory enzymes to promote the formation of free radicals. Such dual characteristics endow zinc ions with unparalleled advantages in the direction of antibacterial therapy. Based on the fascinating features of zinc ions, nanomaterial-based zinc ion interference therapy emerges relying on the outstanding benefits of nanomaterials. Zinc ion interference therapy is divided into two classes: zinc overloading and zinc deprivation. In this review, we summarized the recent innovative zinc ion interference strategy for the treatment of bacterial infections and focused on analyzing the antibacterial mechanism of zinc overloading and zinc deprivation. Finally, we discuss the current limitations of zinc ion interference antibacterial therapy and put forward problems of clinical translation for zinc ion interference antibacterial therapy.
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Affiliation(s)
- Yongbin Wei
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Jiaming Wang
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Sixuan Wu
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Ruixue Zhou
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Kaixiang Zhang
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
- Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, Zhengzhou, China
- Key Laboratory of Key Drug Preparation Technology Ministry of Education, Zhengzhou University, Zhengzhou, China
| | - Zhenzhong Zhang
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
- Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, Zhengzhou, China
- Key Laboratory of Key Drug Preparation Technology Ministry of Education, Zhengzhou University, Zhengzhou, China
| | - Junjie Liu
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
- Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, Zhengzhou, China
- Key Laboratory of Key Drug Preparation Technology Ministry of Education, Zhengzhou University, Zhengzhou, China
| | - Shangshang Qin
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
- Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, Zhengzhou, China
- Key Laboratory of Key Drug Preparation Technology Ministry of Education, Zhengzhou University, Zhengzhou, China
| | - Jinjin Shi
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
- Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, Zhengzhou, China
- Key Laboratory of Key Drug Preparation Technology Ministry of Education, Zhengzhou University, Zhengzhou, China
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23
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Linolenic Acid-Metronidazole: a Compound Relieving Drug Resistance and Inhibiting Helicobacter pylori. Antimicrob Agents Chemother 2022; 66:e0007322. [PMID: 35758720 PMCID: PMC9295599 DOI: 10.1128/aac.00073-22] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Metronidazole (Met) is the first choice for treating Helicobacter pylori (Hp). However, Hp is easy to resistant, making Met unable to be widely used. How to overcome Hp’s Met resistance is still an issue. In this study, Met was used as the primary raw material with linolenic acid to prepare a novel compound-linolenic acid-metronidazole (Lla-Met). The MIC, minimum bactericidal concentration (MBC), colonization amount of Hp in gastric mucosa, etc., were evaluated, respectively. Lla-Met was successfully prepared by the detection of nuclear magnetic resonance, etc., and its MIC and MBC to Hp were 2~4 μg/mL, 8~16 μg/mL. Moreover, in vivo experiments, Lla-Met significantly reduced the colonization of drug-resistant Hp in gastric mucosa. In the toxicity test, Lla-Met inhibited rate to GES-1 and BGC823 cells were 15% at 128 μg/mL; the mice were administered 10 times treatment Lla-Met treatment (240 mg/kg), have no difference significant injuries were found in their stomach, liver, spleen, kidney, and weight. In addition, Hp G27 continued for 18 days in vitro with sub-Lla-Met concentration, G27 did not show drug resistance to Lla-Met; Lla-Met did not exert an effect on non-Hp species with 128 μg/mL; Compared with a neutral environment, when the acid concentration is 3.0, Lla-Met is not decomposed and has better stability. Conclusion: Lla-Met, a newly prepared compound, has relatively well antibacterial of Met-resistant and sensitive Hp, with a capability of overcoming the metronidazole resistance of Hp.
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Wang Y, Wu S, Wang L, Wang Y, Liu D, Fu Y, Xie Y. The Activity of Liposomal Linolenic Acid Against Helicobacter pylori In Vitro and Its Impact on Human Fecal Bacteria. Front Cell Infect Microbiol 2022; 12:865320. [PMID: 35656035 PMCID: PMC9152453 DOI: 10.3389/fcimb.2022.865320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Accepted: 04/13/2022] [Indexed: 11/13/2022] Open
Abstract
Helicobacter pylori (H. pylori) infection is associated with a variety of gastrointestinal diseases. Here, we focused on the activity of a novel nanomedicine-liposomal linolenic acid (LipoLLA) against H. pylori and its impact on human fecal bacteria in vitro. The minimum inhibitory concentrations (MICs) of LipoLLA against 30 H. pylori clinical strains were determined in combination with amoxicillin (AMX), metronidazole (MTZ), levofloxacin (LVFX) and clarithromycin (CAM). Bactericidal activity was measured by generating concentration-bactericidal curves at different times and pH values. Leakage of glucose (GLU) and aspartate aminotransferase (AST) was detected, combined with detection of changes in morphology by electron microscopy, to study the mechanism of action of LipoLLA against H. pylori. The effect of LipoLLA on human fecal bacteria was studied by high-throughput sequencing of fecal samples. We observed a synergistic or additive effect when LipoLLA was combined with AMX, MTZ, LVFX and CAM. The concentration-sterilization curves were pH and time dependent. After treatment with LipoLLA, GLU and AST levels were increased (P<0.05), and the morphology of H. pylori changed significantly. Moreover, LipoLLA activity led to no significant changes in the intestinal flora in terms of alpha diversity, species composition, beta diversity, etc. In conclusion, LipoLLA showed good anti-H. pylori effects. It destroyed the outer membrane barrier and caused leakage of the bacterial contents to achieve anti-H. pylori effects. And LipoLLA had little effect on human fecal bacteria in vitro.
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Affiliation(s)
- Ya Wang
- Key Laboratory of Digestive Diseases of Jiangxi, Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- School of Pharmacy, Nanchang University, Nanchang, China
| | - Shuang Wu
- Key Laboratory of Digestive Diseases of Jiangxi, Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Le Wang
- Key Laboratory of Digestive Diseases of Jiangxi, Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Youhua Wang
- Key Laboratory of Digestive Diseases of Jiangxi, Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Dongsheng Liu
- Key Laboratory of Digestive Diseases of Jiangxi, Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yingjun Fu
- School of Pharmacy, Nanchang University, Nanchang, China
| | - Yong Xie
- Key Laboratory of Digestive Diseases of Jiangxi, Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- *Correspondence: Yong Xie,
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Delahunty I, Li J, Jiang W, Lee C, Yang X, Kumar A, Liu Z, Zhang W, Xie J. 7-Dehydrocholesterol Encapsulated Polymeric Nanoparticles As a Radiation-Responsive Sensitizer for Enhancing Radiation Therapy. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2022; 18:e2200710. [PMID: 35304816 PMCID: PMC9068268 DOI: 10.1002/smll.202200710] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 02/25/2022] [Indexed: 06/14/2023]
Abstract
Therapeutics that can be activated by radiation in situ to enhance the efficacy of radiotherapy are highly desirable. Herein, 7-Dehydrocholesterol (7-DHC), a biosynthetic precursor of cholesterol, as a radiosensitizer, exploiting its ability to propagate the free radical chain reaction is explored. The studies show that 7-DHC can react with radiation-induced reactive oxygen species and in turn promote lipid peroxidation, double-strand breaks, and mitochondrial damage in cancer cells. For efficient delivery, 7-DHC is encapsulated into poly(lactic-co-glycolic acid) nanoparticles, forming 7-DHC@PLGA NPs. When tested in CT26 tumor bearing mice, 7-DHC@PLGA NPs significantly enhanced the efficacy of radiotherapy, causing complete tumor eradication in 30% of the treated animals. After treatment, 7-DHC is converted to cholesterol, causing no detectable side effects or hypercalcemia. 7-DHC@PLGA NPs represent a radiation-responsive sensitizer with great potential in clinical translation.
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Affiliation(s)
- Ian Delahunty
- Department of Chemistry, University of Georgia, Athens, GA, 30602, USA
| | - Jianwen Li
- Department of Chemistry, University of Georgia, Athens, GA, 30602, USA
| | - Wen Jiang
- Department of Chemistry, University of Georgia, Athens, GA, 30602, USA
| | - Chaebin Lee
- Department of Chemistry, University of Georgia, Athens, GA, 30602, USA
| | - Xueyuan Yang
- Department of Chemistry, University of Georgia, Athens, GA, 30602, USA
| | - Anil Kumar
- Department of Chemistry, University of Georgia, Athens, GA, 30602, USA
| | - Zhi Liu
- Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA, 30602, USA
| | - Weizhong Zhang
- Department of Chemistry, University of Georgia, Athens, GA, 30602, USA
| | - Jin Xie
- Department of Chemistry, University of Georgia, Athens, GA, 30602, USA
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Deng G, Wu Y, Song Z, Li S, Du M, Deng J, Xu Q, Deng L, Bahlol HS, Han H. Tea Polyphenol Liposomes Overcome Gastric Mucus to Treat Helicobacter Pylori Infection and Enhance the Intestinal Microenvironment. ACS APPLIED MATERIALS & INTERFACES 2022; 14:13001-13012. [PMID: 35266695 DOI: 10.1021/acsami.1c23342] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Infection with Helicobacter pylori (Hp) is one of the leading causes of stomach cancer. The ability to treat Hp infection is hampered by a lack of stomach gastric acid environment. This work introduces a nanoliposome that can rapidly adjust the gastric acid environment to ensure a drug's optimal efficacy. We introduce CaCO3@Fe-TP@EggPC nanoliposomes (CTE NLs) that are composed of Fe3+ and tea polyphenols (TPs) forming complexes on the surface of internal CaCO3 and then with lecithin producing a phospholipid bilayer on the polyphenols' outer surface. Through the action of iron-TP chelate, the phospholipid layer can fuse with the bacterial membrane to eliminate Hp. Furthermore, CaCO3 can promptly consume the excessive gastric acid, ensuring an ideal operating environment for the chelate. TPs, on the other hand, can improve the inflammation and gut microbes in the body. The experimental results show that CTE NLs can quickly consume protons in the stomach and reduce the bacterial burden by 1.2 orders of magnitude while reducing the inflammatory factors in the body. The biosafety evaluation revealed that nanoliposomes have good biocompatibility and provide a new strategy for treating Hp infection.
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Affiliation(s)
- Guiyun Deng
- State Key Laboratory of Agriculture Microbiology, College of Life Science and Technology Huazhong Agricultural University, Wuhan 430070, China
| | - Yang Wu
- State Key Laboratory of Agriculture Microbiology, College of Life Science and Technology Huazhong Agricultural University, Wuhan 430070, China
| | - Zhiyong Song
- State Key Laboratory of Agriculture Microbiology, College of Science Huazhong Agricultural University, Wuhan 430070, China
| | - Shuojun Li
- State Key Laboratory of Agriculture Microbiology, College of Life Science and Technology Huazhong Agricultural University, Wuhan 430070, China
| | - Moqing Du
- State Key Laboratory of Agriculture Microbiology, College of Science Huazhong Agricultural University, Wuhan 430070, China
| | - Jiamin Deng
- State Key Laboratory of Agriculture Microbiology, College of Life Science and Technology Huazhong Agricultural University, Wuhan 430070, China
| | - Quan Xu
- State Key Laboratory of Agriculture Microbiology, College of Science Huazhong Agricultural University, Wuhan 430070, China
| | - Liu Deng
- State Key Laboratory of Agriculture Microbiology, College of Life Science and Technology Huazhong Agricultural University, Wuhan 430070, China
| | - Hagar Shendy Bahlol
- State Key Laboratory of Agriculture Microbiology, College of Life Science and Technology Huazhong Agricultural University, Wuhan 430070, China
- Department of Biochemistry, Faculty of Agriculture, Benha University, Moshtohor, Toukh 13736, Egypt
| | - Heyou Han
- State Key Laboratory of Agriculture Microbiology, College of Life Science and Technology Huazhong Agricultural University, Wuhan 430070, China
- State Key Laboratory of Agriculture Microbiology, College of Science Huazhong Agricultural University, Wuhan 430070, China
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27
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Yan LX, Wang BB, Zhao X, Chen LJ, Yan XP. A pH-Responsive Persistent Luminescence Nanozyme for Selective Imaging and Killing of Helicobacter pylori and Common Resistant Bacteria. ACS APPLIED MATERIALS & INTERFACES 2021; 13:60955-60965. [PMID: 34904434 DOI: 10.1021/acsami.1c21318] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Helicobacter pylori (H. pylori) infection is implicated in the etiology of many diseases. H. pylori eradication by antibiotic therapy is limited by the extreme acidic environment in the stomach, the undesired side effect of intestinal commensal bacteria, and the development of drug resistance. Here, we report a pH-responsive persistent luminescence (PL) nanozyme (MSPLNP-Au-CB) for in vivo imaging and inactivation of H. pylori. This PL nanozyme is composed of mesoporous silica (MS)-coated persistent luminescence nanoparticles (MSPLNP), Au nanoparticles (AuNP), and chitosan-benzeneboronic acid (CB), taking advantage of the long PL of PLNP to realize autofluorescence-free imaging, the pH-activated oxidase- and peroxidase-like nanozyme activity of AuNP, and the bacterial binding capacity of CB. The MSPLNP-Au-CB nanozyme can resist the corrosion of gastric acid and exhibit pH-activated dual nanozyme activity to catalyze bactericidal reactive oxygen species generation. This multifunctional nanozyme enables targeted imaging and activated deactivation of H. pylori under extreme gastric acid conditions as well as methicillin-resistant Staphylococcus aureus in common slightly acidic environments, while it has no side effects on the commensal bacteria and normal cells in normal physiological environments. This work provides a promising PL nanozyme platform for bioimaging and therapy of bacterial infection under harsh conditions.
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Affiliation(s)
- Li-Xia Yan
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- International Joint Laboratory on Food Safety, Jiangnan University, Wuxi 214122, China
- Institute of Analytical Food Safety, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Bei-Bei Wang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- International Joint Laboratory on Food Safety, Jiangnan University, Wuxi 214122, China
- Institute of Analytical Food Safety, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Xu Zhao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- International Joint Laboratory on Food Safety, Jiangnan University, Wuxi 214122, China
- Institute of Analytical Food Safety, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Li-Jian Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- International Joint Laboratory on Food Safety, Jiangnan University, Wuxi 214122, China
- Institute of Analytical Food Safety, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Xiu-Ping Yan
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- International Joint Laboratory on Food Safety, Jiangnan University, Wuxi 214122, China
- Institute of Analytical Food Safety, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, Jiangnan University, Wuxi 214122, China
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Arif M, Sharaf M, Samreen, Dong Q, Wang L, Chi Z, Liu CG. Bacteria-targeting chitosan/carbon dots nanocomposite with membrane disruptive properties improve eradication rate of Helicobacter pylori. JOURNAL OF BIOMATERIALS SCIENCE. POLYMER EDITION 2021; 32:2423-2447. [PMID: 34644235 DOI: 10.1080/09205063.2021.1972559] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Revised: 08/21/2021] [Accepted: 08/23/2021] [Indexed: 10/20/2022]
Abstract
We designed a bacteria-targeting and membrane disrupting nanocomposite for successful antibiotic treatment of Helicobacter pylori (H. pylori) infections in the present study. The antibacterial nanocomposite was prepared from thiolated-ureido-chitosan (Cys-U-CS) and anionic poly (malic acid) (PMLA) via electrostatic interaction decorated with dual functional ammonium citrate carbon quantum dots (CDs). Cys-U-CS serves as a targeting building block for attaching antibacterial nanocomposite onto bacterial cell surface through Urel-mediated protein channel. Simultaneously, membrane disrupting CDs generate ROS and lyse the bacterial outer membrane, allowing antibiotics to enter the intracellular cytoplasm. As a result, Cys-U-CS/PMLA@CDs nanocomposite (UCPM-NPs) loaded with the antibiotic amoxicillin (AMX) not only effectively target and kill bacteria in vitro via Urel-mediated adhesion but also efficiently retain in the stomach where H. pylori reside, serving as an effective drug carrier for abrupt on-site release of AMX into the bacterial cytoplasm. Furthermore, since thiolated-chitosan has a mucoadhesive property, UCPM-NPs may adhere to the stomach mucus layer and pass through it swiftly. According to our results, bacterial targeting is crucial for guaranteeing successful antibiotic treatment. The bacteria targeting UCPM-NPs with membrane disruptive ability may establish a promising drug delivery system for the effective targeted delivery of antibiotics to treat H. pylori infections.
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Affiliation(s)
- Muhammad Arif
- College of Marine Life Science, Ocean University Of China, Qingdao, P.R. China
| | - Mohamed Sharaf
- College of Marine Life Science, Ocean University Of China, Qingdao, P.R. China
- Department of Biochemistry, Faculty of Agriculture, Al-Azhar University, Cairo, Egypt
| | - Samreen
- College of Marine Life Science, Ocean University Of China, Qingdao, P.R. China
| | - Quanjiang Dong
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao, P.R. China
| | - Lili Wang
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao, P.R. China
| | - Zhe Chi
- College of Marine Life Science, Ocean University Of China, Qingdao, P.R. China
| | - Chen-Guang Liu
- College of Marine Life Science, Ocean University Of China, Qingdao, P.R. China
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Khan S, Sharaf M, Ahmed I, Khan TU, Shabana S, Arif M, Kazmi SSUH, Liu C. Potential utility of nano-based treatment approaches to address the risk of Helicobacter pylori. Expert Rev Anti Infect Ther 2021; 20:407-424. [PMID: 34658307 DOI: 10.1080/14787210.2022.1990041] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Helicobacter pylori (H. pylori) has occupied a significant place among infectious pathogens and it has been documented as a leading challenge due to its higher resistance to the commonly used drugs, higher adaptability, and lower targeting specificity of the available drugs. AREAS COVERED New treatment strategies are urgently needed in order to improve the current advancement in modern medicine. Nanocarriers have gained an advantage of drug encapsulation and high retention time in the stomach with a prolonged drug release rate at the targeted site. This article aims to highlight the recent advances in nanotechnology with special emphasis on metallic, polymeric, lipid, membrane coated, and target-specific nanoparticles (NPs), as well as, natural products for treating H. pylori infection. We discussed a comprehensive approach to understand H. pylori infection and elicits to rethink about the increasing threat posed by H. pylori and its treatment strategies. EXPERT OPINION To address these issues, nanotechnology has got huge potential to combat H. pylori infection and has made great progress in the field of biomedicine. Moreover, combinatory studies of natural products and probiotics in conjugation with NPs have proven efficiency against H. pylori infection, with an advantage of lower cytotoxicity, minimal side effects, and stronger antibacterial potential.[Figure: see text].
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Affiliation(s)
- Sohaib Khan
- Department of Biochemistry and Molecular Biology, College of Marine Life Sciences, Ocean University of China, Qingdao, China
| | - Mohamed Sharaf
- Department of Biochemistry and Molecular Biology, College of Marine Life Sciences, Ocean University of China, Qingdao, China.,Department of Biochemistry, Faculty of Agriculture, AL-Azhar University, Nasr City, Egypt
| | | | | | - Samah Shabana
- Department of Biochemistry and Molecular Biology, College of Marine Life Sciences, Ocean University of China, Qingdao, China
| | - Muhammad Arif
- Department of Biochemistry and Molecular Biology, College of Marine Life Sciences, Ocean University of China, Qingdao, China
| | | | - Chenguang Liu
- Department of Biochemistry and Molecular Biology, College of Marine Life Sciences, Ocean University of China, Qingdao, China
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30
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Noronha BP, Mambrini JVDM, Torres KCL, Martins-Filho OA, Teixeira-Carvalho A, Lima-Costa MF, Peixoto SV. Chlamydia pneumoniae and Helicobacter pylori infections and immunological profile of community-dwelling older adults. Exp Gerontol 2021; 156:111589. [PMID: 34637947 DOI: 10.1016/j.exger.2021.111589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 10/04/2021] [Accepted: 10/05/2021] [Indexed: 11/29/2022]
Abstract
Chronic bacterial infections are associated with changes in the immunosenescence process and immunological biomarkers can assist in monitoring these changes. The identification of this immunological profile is important because Chlamydia pneumoniae (C. pneumoniae) and Helicobacter pylori (H. pylori) infections are important factors of morbidity and mortality among the older adults. This study aimed to identify changes in the immunological profile in the presence of C. pneumoniae and H. pylori infections among community-dwelling older adults. This is a cross-sectional study that used data from 1432 participants from the Bambuí Cohort Study of Aging, Minas Gerais, Brazil. The presence of immunoglobulin G (IgG) for C. pneumoniae and H. pylori was considered a dependent variable and assessed in the participants' serum using the enzyme-linked immunosorbent assay (ELISA). In assessing the immunological profile, the following inflammatory markers were considered: CXCL8, CXCL9, CXCL10, CCL2, CCL5, IL-1β, IL-6, IL-10, IL-12, TNF, and CRP. Associations were assessed by logistic regression, estimating odds ratios and confidence intervals (95%) using the Stata® V.13.1 software. The seroprevalence of anti-C. pneumoniae and anti-H. pylori antibodies was 55.9% and 70.3%, respectively. While high levels of anti-C. pneumoniae antibodies were associated with higher concentrations of CXCL10 and IL-10, higher levels of IL-1β and IL-6 were inversely associated with the titration of anti-H. pylori antibodies. The results characterize immunological profiles associated with these chronic infections and reinforce the potential effects of biomarkers on infections by these bacteria and on the immunosenescence process.
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Affiliation(s)
- Beatriz Prado Noronha
- Instituto René Rachou, Fundação Oswaldo Cruz, Fiocruz Minas, Núcleo de Estudos em Saúde Pública e Envelhecimento, Belo Horizonte, MG, Brazil
| | - Juliana Vaz de Melo Mambrini
- Instituto René Rachou, Fundação Oswaldo Cruz, Fiocruz Minas, Núcleo de Estudos em Saúde Pública e Envelhecimento, Belo Horizonte, MG, Brazil.
| | - Karen Cecília Lima Torres
- Instituto René Rachou, Fundação Oswaldo Cruz, Fiocruz Minas, Grupo Integrado de Pesquisas em Biomarcadores, Belo Horizonte, MG, Brazil; Universidade José do Rosário Vellano, UNIFENAS, Belo Horizonte, MG, Brazil
| | - Olindo Assis Martins-Filho
- Instituto René Rachou, Fundação Oswaldo Cruz, Fiocruz Minas, Grupo Integrado de Pesquisas em Biomarcadores, Belo Horizonte, MG, Brazil.
| | - Andréa Teixeira-Carvalho
- Instituto René Rachou, Fundação Oswaldo Cruz, Fiocruz Minas, Grupo Integrado de Pesquisas em Biomarcadores, Belo Horizonte, MG, Brazil.
| | - Maria Fernanda Lima-Costa
- Instituto René Rachou, Fundação Oswaldo Cruz, Fiocruz Minas, Núcleo de Estudos em Saúde Pública e Envelhecimento, Belo Horizonte, MG, Brazil.
| | - Sérgio Viana Peixoto
- Instituto René Rachou, Fundação Oswaldo Cruz, Fiocruz Minas, Núcleo de Estudos em Saúde Pública e Envelhecimento, Belo Horizonte, MG, Brazil; Universidade Federal de Minas Gerais, Escola de Enfermagem, Departamento de Gestão em Saúde, Belo Horizonte, MG, Brazil.
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Cardos IA, Zaha DC, Sindhu RK, Cavalu S. Revisiting Therapeutic Strategies for H. pylori Treatment in the Context of Antibiotic Resistance: Focus on Alternative and Complementary Therapies. Molecules 2021; 26:molecules26196078. [PMID: 34641620 PMCID: PMC8512130 DOI: 10.3390/molecules26196078] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 10/01/2021] [Accepted: 10/02/2021] [Indexed: 12/15/2022] Open
Abstract
The prevalence of Helicobacter pylori infection remains significant worldwide and it depends on many factors: gender, age, socio-economic status, geographic area, diet, and lifestyle. All successful infectious diseases treatments use antibiotic-susceptibility testing, but this strategy is not currently practical for H. pylori and the usual cure rates of H. pylori are lower than other bacterial infections. Actually, there is no treatment that ensures complete eradication of this pathogen. In the context of an alarming increase in resistance to antibiotics (especially to clarithromycin and metronidazole), alternative and complementary options and strategies are taken into consideration. As the success of antibacterial therapy depends not only on the susceptibility to given drugs, but also on the specific doses, formulations, use of adjuvants, treatment duration, and reinfection rates, this review discusses the current therapies for H. pylori treatment along with their advantages and limitations. As an alternative option, this work offers an extensively referenced approach on natural medicines against H. pylori, including the significance of nanotechnology in developing new strategies for treatment of H. pylori infection.
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Affiliation(s)
- Ioana Alexandra Cardos
- Faculty of Medicine and Pharmacy, Doctoral School of Biomedical Sciences, University of Oradea, 1 University Street, 410087 Oradea, Romania;
| | - Dana Carmen Zaha
- Department of Preclinical Sciences, Faculty of Medicine and Pharmacy, University of Oradea, 1 University Street, 410087 Oradea, Romania
- Correspondence: (D.C.Z.); (R.K.S.); (S.C.)
| | - Rakesh K. Sindhu
- Chitkara College of Pharmacy, Chitkara University, Chandigarh 140401, India
- Correspondence: (D.C.Z.); (R.K.S.); (S.C.)
| | - Simona Cavalu
- Department of Preclinical Sciences, Faculty of Medicine and Pharmacy, University of Oradea, 1 University Street, 410087 Oradea, Romania
- Correspondence: (D.C.Z.); (R.K.S.); (S.C.)
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Shi Y, Feng X, Lin L, Wang J, Chi J, Wu B, Zhou G, Yu F, Xu Q, Liu D, Quan G, Lu C, Pan X, Cai J, Wu C. Virus-inspired surface-nanoengineered antimicrobial liposome: A potential system to simultaneously achieve high activity and selectivity. Bioact Mater 2021; 6:3207-3217. [PMID: 33723524 PMCID: PMC7947718 DOI: 10.1016/j.bioactmat.2021.02.038] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Revised: 02/11/2021] [Accepted: 02/28/2021] [Indexed: 01/06/2023] Open
Abstract
Enveloped viruses such as SARS-CoV-2 frequently have a highly infectious nature and are considered effective natural delivery systems exhibiting high efficiency and specificity. Since simultaneously enhancing the activity and selectivity of lipopeptides is a seemingly unsolvable problem for conventional chemistry and pharmaceutical approaches, we present a biomimetic strategy to construct lipopeptide-based mimics of viral architectures and infections to enhance their antimicrobial efficacy while avoiding side effects. Herein, a surface-nanoengineered antimicrobial liposome (SNAL) is developed with the morphological features of enveloped viruses, including a moderate size range, lipid-based membrane structure, and highly lipopeptide-enriched bilayer surface. The SNAL possesses virus-like infection to bacterial cells, which can mediate high-efficiency and high-selectivity bacteria binding, rapidly attack and invade bacteria via plasma membrane fusion pathway, and induce a local "burst" release of lipopeptide to produce irreversible damage of cell membrane. Remarkably, viral mimics are effective against multiple pathogens with low minimum inhibitory concentrations (1.6-6.3 μg mL-1), high bactericidal efficiency of >99% within 2 h, >10-fold enhanced selectivity over free lipopeptide, 99.8% reduction in skin MRSA load after a single treatment, and negligible toxicity. This bioinspired design has significant potential to enhance the therapeutic efficacy of lipopeptides and may create new opportunities for designing next-generation antimicrobials.
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Affiliation(s)
- Yin Shi
- College of Pharmacy, Jinan University, Guangzhou, Guangdong, 511443, China
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong, 510006, China
| | - Xiaoqian Feng
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong, 510006, China
| | - Liming Lin
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong, 510006, China
| | - Jing Wang
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong, 510006, China
| | - Jiaying Chi
- College of Pharmacy, Jinan University, Guangzhou, Guangdong, 511443, China
| | - Biyuan Wu
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong, 510006, China
| | - Guilin Zhou
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong, 510006, China
| | - Feiyuan Yu
- Medical College, Shantou University, Shantou, Guangdong, 15041, China
| | - Qian Xu
- Medical College, Shantou University, Shantou, Guangdong, 15041, China
| | - Daojun Liu
- Medical College, Shantou University, Shantou, Guangdong, 15041, China
| | - Guilan Quan
- College of Pharmacy, Jinan University, Guangzhou, Guangdong, 511443, China
| | - Chao Lu
- College of Pharmacy, Jinan University, Guangzhou, Guangdong, 511443, China
- Department of Chemistry, University of South Florida, Tampa, FL, 33620, United States
| | - Xin Pan
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong, 510006, China
| | - Jianfeng Cai
- Department of Chemistry, University of South Florida, Tampa, FL, 33620, United States
| | - Chuanbin Wu
- College of Pharmacy, Jinan University, Guangzhou, Guangdong, 511443, China
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White B, Sterrett JD, Grigoryan Z, Lally L, Heinze JD, Alikhan H, Lowry CA, Perez LJ, DeSipio J, Phadtare S. Characterization of gut microbiome and metabolome in Helicobacter pylori patients in an underprivileged community in the United States. World J Gastroenterol 2021; 27:5575-5594. [PMID: 34588753 PMCID: PMC8433610 DOI: 10.3748/wjg.v27.i33.5575] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 07/02/2021] [Accepted: 08/13/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori), a bacterium that infects approximately half of the world's population, is associated with various gastrointestinal diseases, including peptic ulcers, non-ulcer dyspepsia, gastric adenocarcinoma, and gastric lymphoma. As the burden of antibiotic resistance increases, the need for new adjunct therapies designed to facilitate H. pylori eradication and reduce negative distal outcomes associated with infection has become more pressing. Characterization of the interactions between H. pylori, the fecal microbiome, and fecal fatty acid metabolism, as well as the mechanisms underlying these interactions, may offer new therapeutic approaches. AIM To characterize the gut microbiome and metabolome in H. pylori patients in a socioeconomically challenged and underprivileged inner-city community. METHODS Stool samples from 19 H. pylori patients and 16 control subjects were analyzed. 16S rRNA gene sequencing was performed on normalized pooled amplicons using the Illumina MiSeq System using a MiSeq reagent kit v2. Alpha and beta diversity analyses were performed in QIIME 2. Non-targeted fatty acid analysis of the samples was carried out using gas chromatography-mass spectrometry, which measures the total content of 30 fatty acids in stool after conversion into their corresponding fatty acid methyl esters. Multi-dimensional scaling (MDS) was performed on Bray-Curtis distance matrices created from both the metabolomics and microbiome datasets and a Procrustes test was performed on the metabolomics and microbiome MDS coordinates. RESULTS Fecal microbiome analysis showed that alpha diversity was lowest in H. pylori patients over 40 years of age compared to control subjects of similar age group. Beta diversity analysis of the samples revealed significant differences in microbial community structure between H. pylori patients and control subjects across all ages. Thirty-eight and six taxa had lower and higher relative abundance in H. pylori patients, respectively. Taxa that were enriched in H. pylori patients included Atopobium, Gemellaceae, Micrococcaceae, Gemellales and Rothia (R. mucilaginosa). Notably, relative abundance of the phylum Verrucomicrobia was decreased in H. pylori patients compared to control subjects. Procrustes analysis showed a significant relationship between the microbiome and metabolome datasets. Stool samples from H. pylori patients showed increases in several fatty acids including the polyunsaturated fatty acids (PUFAs) 22:4n6, 22:5n3, 20:3n6 and 22:2n6, while decreases were noted in other fatty acids including the PUFA 18:3n6. The pattern of changes in fatty acid concentration correlated to the Bacteroidetes:Firmicutes ratio determined by 16S rRNA gene analysis. CONCLUSION This exploratory study demonstrates H. pylori-associated changes to the fecal microbiome and fecal fatty acid metabolism. Such changes may have implications for improving eradication rates and minimizing associated negative distal outcomes.
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Affiliation(s)
- Brian White
- Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ 08103, United States
| | - John D Sterrett
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, United States
| | - Zoya Grigoryan
- Department of Internal Medicine, Lenox Hill Hospital, NYC, NY 10075, United States
| | - Lauren Lally
- Department of Internal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, United States
| | - Jared D Heinze
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, United States
| | - Hyder Alikhan
- Department of Biological Sciences, Rowan University, Glassboro, NJ 08028, United States
| | - Christopher A Lowry
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, United States
| | - Lark J Perez
- Department of Chemistry and Biochemistry, Rowan University, Glassboro, NJ 08028, United States
| | - Joshua DeSipio
- Department of Gastroenterology, Cooper University Hospital, Camden, NJ 08103, United States
| | - Sangita Phadtare
- Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ 08103, United States
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Tan JYB, Yoon BK, Cho NJ, Lovrić J, Jug M, Jackman JA. Lipid Nanoparticle Technology for Delivering Biologically Active Fatty Acids and Monoglycerides. Int J Mol Sci 2021; 22:9664. [PMID: 34575831 PMCID: PMC8465605 DOI: 10.3390/ijms22189664] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2021] [Revised: 09/03/2021] [Accepted: 09/05/2021] [Indexed: 12/12/2022] Open
Abstract
There is enormous interest in utilizing biologically active fatty acids and monoglycerides to treat phospholipid membrane-related medical diseases, especially with the global health importance of membrane-enveloped viruses and bacteria. However, it is difficult to practically deliver lipophilic fatty acids and monoglycerides for therapeutic applications, which has led to the emergence of lipid nanoparticle platforms that support molecular encapsulation and functional presentation. Herein, we introduce various classes of lipid nanoparticle technology and critically examine the latest progress in utilizing lipid nanoparticles to deliver fatty acids and monoglycerides in order to treat medical diseases related to infectious pathogens, cancer, and inflammation. Particular emphasis is placed on understanding how nanoparticle structure is related to biological function in terms of mechanism, potency, selectivity, and targeting. We also discuss translational opportunities and regulatory needs for utilizing lipid nanoparticles to deliver fatty acids and monoglycerides, including unmet clinical opportunities.
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Affiliation(s)
- Jia Ying Brenda Tan
- School of Chemical Engineering and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea; (J.Y.B.T.); (B.K.Y.)
- School of Materials Science and Engineering, Nanyang Technological University, Singapore 637553, Singapore;
| | - Bo Kyeong Yoon
- School of Chemical Engineering and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea; (J.Y.B.T.); (B.K.Y.)
- School of Healthcare and Biomedical Engineering, Chonnam National University, Yeosu 59626, Korea
| | - Nam-Joon Cho
- School of Materials Science and Engineering, Nanyang Technological University, Singapore 637553, Singapore;
| | - Jasmina Lovrić
- Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia; (J.L.); (M.J.)
| | - Mario Jug
- Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia; (J.L.); (M.J.)
| | - Joshua A. Jackman
- School of Chemical Engineering and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea; (J.Y.B.T.); (B.K.Y.)
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Zhang X, Chen X, Guo Y, Gao G, Wang D, Wu Y, Liu J, Liang G, Zhao Y, Wu FG. Dual Gate-Controlled Therapeutics for Overcoming Bacterium-Induced Drug Resistance and Potentiating Cancer Immunotherapy. Angew Chem Int Ed Engl 2021; 60:14013-14021. [PMID: 33768682 DOI: 10.1002/anie.202102059] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Indexed: 12/20/2022]
Abstract
The presence of bacteria in the tumor can cause cancer resistance to chemotherapeutics. To fight against bacterium-induced drug resistance, herein we design self-traceable nanoreservoirs that are simultaneously loaded with gemcitabine (an anticancer drug) and ciprofloxacin (an antibiotic) and are decorated with hyaluronic acid for active tumor targeting. The nanoreservoirs have a pH-sensitive gate and an enzyme-responsive gate that can be opened in the acidic and hyaluronidase-abundant tumor microenvironment to control drug release rates. Moreover, the nanoreservoirs can specifically target the tumor regions without eliciting evident toxicity to normal tissues, kill the intratumoral bacteria, and inhibit the tumor growth even in the presence of the bacteria. Unexpectedly, the nanoreservoirs can activate T cell-mediated immune responses through promoting antigen-presenting dendritic cell maturation and depleting immunosuppressive myeloid-derived suppressor cells in bacterium-infected tumors.
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Affiliation(s)
- Xiaodong Zhang
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China.,Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371, Singapore, Singapore
| | - Xiaokai Chen
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China.,Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371, Singapore, Singapore
| | - Yuxin Guo
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Ge Gao
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Dongdong Wang
- Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371, Singapore, Singapore
| | - Yinglong Wu
- Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371, Singapore, Singapore
| | - Jiawei Liu
- Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371, Singapore, Singapore
| | - Gaolin Liang
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Yanli Zhao
- Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371, Singapore, Singapore
| | - Fu-Gen Wu
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
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Zhang X, Chen X, Guo Y, Gao G, Wang D, Wu Y, Liu J, Liang G, Zhao Y, Wu F. Dual Gate‐Controlled Therapeutics for Overcoming Bacterium‐Induced Drug Resistance and Potentiating Cancer Immunotherapy. Angew Chem Int Ed Engl 2021. [DOI: 10.1002/ange.202102059] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Affiliation(s)
- Xiaodong Zhang
- State Key Laboratory of Bioelectronics School of Biological Science and Medical Engineering Southeast University Nanjing 210096 China
- Division of Chemistry and Biological Chemistry School of Physical and Mathematical Sciences Nanyang Technological University 21 Nanyang Link 637371 Singapore Singapore
| | - Xiaokai Chen
- State Key Laboratory of Bioelectronics School of Biological Science and Medical Engineering Southeast University Nanjing 210096 China
- Division of Chemistry and Biological Chemistry School of Physical and Mathematical Sciences Nanyang Technological University 21 Nanyang Link 637371 Singapore Singapore
| | - Yuxin Guo
- State Key Laboratory of Bioelectronics School of Biological Science and Medical Engineering Southeast University Nanjing 210096 China
| | - Ge Gao
- State Key Laboratory of Bioelectronics School of Biological Science and Medical Engineering Southeast University Nanjing 210096 China
| | - Dongdong Wang
- Division of Chemistry and Biological Chemistry School of Physical and Mathematical Sciences Nanyang Technological University 21 Nanyang Link 637371 Singapore Singapore
| | - Yinglong Wu
- Division of Chemistry and Biological Chemistry School of Physical and Mathematical Sciences Nanyang Technological University 21 Nanyang Link 637371 Singapore Singapore
| | - Jiawei Liu
- Division of Chemistry and Biological Chemistry School of Physical and Mathematical Sciences Nanyang Technological University 21 Nanyang Link 637371 Singapore Singapore
| | - Gaolin Liang
- State Key Laboratory of Bioelectronics School of Biological Science and Medical Engineering Southeast University Nanjing 210096 China
| | - Yanli Zhao
- Division of Chemistry and Biological Chemistry School of Physical and Mathematical Sciences Nanyang Technological University 21 Nanyang Link 637371 Singapore Singapore
| | - Fu‐Gen Wu
- State Key Laboratory of Bioelectronics School of Biological Science and Medical Engineering Southeast University Nanjing 210096 China
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In vivo activation of pH-responsive oxidase-like graphitic nanozymes for selective killing of Helicobacter pylori. Nat Commun 2021; 12:2002. [PMID: 33790299 PMCID: PMC8012368 DOI: 10.1038/s41467-021-22286-x] [Citation(s) in RCA: 104] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 02/26/2021] [Indexed: 12/19/2022] Open
Abstract
Helicobacter pylori infection is a major etiological factor in gastric diseases. However, clinical antibiotic therapy for H. pylori is limited by continuously decreased therapeutic efficacy and side effects to symbiotic bacteria. Herein, we develop an in vivo activatable pH-responsive graphitic nanozyme, PtCo@Graphene (PtCo@G), for selective treatment of H. pylori. Such nanozymes can resist gastric acid corrosion, exhibit oxidase-like activity to stably generate reactive oxygen species only in acidic gastric milieu and demonstrate superior selective bactericidal property. C18-PEGn-Benzeneboronic acid molecules are modified on PtCo@G, improving its targeting capability. Under acidic gastric pH, graphitic nanozymes show notable bactericidal activity toward H. pylori, while no bacterial killing is observed under intestinal conditions. In mouse model, high antibacterial capability toward H. pylori and negligible side effects toward normal tissues and symbiotic bacteria are achieved. Graphitic nanozyme displays the desired enzyme-like activities at corresponding physiological sites and may address critical issues in clinical treatment of H. pylori infections. Helicobacter pylori is a major cause of gastric diseases, but the standard therapy is limited by continuously decreased therapeutic efficacy and side effects to symbiotic bacteria. Here, the authors develop a pH-responsive graphitic nanozyme that is active under low pH gastric conditions, but inactive in intestines, for selective treatment of H. pylori infections.
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de Souza MPC, de Camargo BAF, Spósito L, Fortunato GC, Carvalho GC, Marena GD, Meneguin AB, Bauab TM, Chorilli M. Highlighting the use of micro and nanoparticles based-drug delivery systems for the treatment of Helicobacter pylori infections. Crit Rev Microbiol 2021; 47:435-460. [PMID: 33725462 DOI: 10.1080/1040841x.2021.1895721] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Due to the high adaptability of Helicobacter pylori and the low targeting specificity of the drugs normally used in pharmacological therapy, the strains are becoming increasingly resistant to these drugs, making it difficult to eradicate the infection. Thus, the search for new therapeutic approaches has been considered urgent. The incorporation of drugs in advanced drug delivery systems, such as nano and microparticles, would allow the improvement of the retention time in the stomach and the prolongation of drug release rates at the target site. Because of this, the present review article aims to highlight the use of micro and nanoparticles as important technological tools for the treatment of H. pylori infections, focussing on the main nanotechnological systems, including nanostructured lipid carriers, liposomes, nanoemulsion, metallic nanoparticles, and polymeric nanoparticles, as well as microtechnological systems such as gastroretentive dosage forms, among them mucoadhesive, magnetic and floating systems were highlighted.
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Affiliation(s)
| | | | - Larissa Spósito
- School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, Brazil São Paulo
| | | | - Gabriela Corrêa Carvalho
- School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, Brazil São Paulo
| | - Gabriel Davi Marena
- School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, Brazil São Paulo
| | | | - Taís Maria Bauab
- School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, Brazil São Paulo
| | - Marlus Chorilli
- School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, Brazil São Paulo
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Wu Y, Song Z, Deng G, Jiang K, Wang H, Zhang X, Han H. Gastric Acid Powered Nanomotors Release Antibiotics for In Vivo Treatment of Helicobacter pylori Infection. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2021; 17:e2006877. [PMID: 33619851 DOI: 10.1002/smll.202006877] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 01/04/2021] [Indexed: 05/18/2023]
Abstract
Helicobacter pylori (H. pylori) infection has ≈75% probability of causing gastric cancer, so it is considered to be the strongest single risk factor for gastric malignancies. However, the harsh gastric acid environment has created obstacles to medical treatment. This work reports a nanomotor with a bottle-shaped container that can be loaded with small molecules of clarithromycin, nano calcium peroxide (CaO2 ), and Pt nanoparticles (Pt NPs) by ultrasound. Nanomotors can quickly consume gastric acid through the chemical reaction of CaO2 to temporarily neutralize gastric acid. The product hydrogen peroxide (H2 O2 ) is catalytically decomposed into a large amount of oxygen (O2 ) by Pt NPs. The local concentration gradient of O2 bubbles causes it to be expelled from the nanobottles through a narrow opening, and then push the nanobottles forward to provide maximum release and prodrug efficacy. Experiments in animal models show that 15 mg nanomotors can safely and quickly neutralize gastric acid in the stomach and simultaneously release prodrugs to achieve good therapeutic effects without causing acute toxicity. H. pylori burden in mice was 2.6 orders of magnitude lower than that in the control group. The stomach returns to normal pH within 1 d after administration.
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Affiliation(s)
- Yang Wu
- State Key Laboratory of Agriculture Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China
| | - Zhiyong Song
- State Key Laboratory of Agriculture Microbiology, College of Science, Huazhong Agricultural University, Wuhan, 430070, China
| | - Guiyun Deng
- State Key Laboratory of Agriculture Microbiology, College of Science, Huazhong Agricultural University, Wuhan, 430070, China
| | - Kai Jiang
- State Key Laboratory of Agriculture Microbiology, College of Science, Huazhong Agricultural University, Wuhan, 430070, China
| | - Huajuan Wang
- State Key Laboratory of Agriculture Microbiology, College of Food Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China
| | - Xueji Zhang
- School of Biomedical Engineering, Shenzhen University, Shenzhen, Guangdong, 518060, China
| | - Heyou Han
- State Key Laboratory of Agriculture Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China
- State Key Laboratory of Agriculture Microbiology, College of Science, Huazhong Agricultural University, Wuhan, 430070, China
- State Key Laboratory of Agriculture Microbiology, College of Food Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China
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Yoon BK, Jeon WY, Sut TN, Cho NJ, Jackman JA. Stopping Membrane-Enveloped Viruses with Nanotechnology Strategies: Toward Antiviral Drug Development and Pandemic Preparedness. ACS NANO 2021; 15:125-148. [PMID: 33306354 DOI: 10.1021/acsnano.0c07489] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/16/2023]
Abstract
Membrane-enveloped viruses are a leading cause of viral epidemics, and there is an outstanding need to develop broad-spectrum antiviral strategies to treat and prevent enveloped virus infections. In this review, we critically discuss why the lipid membrane surrounding enveloped virus particles is a promising antiviral target and cover the latest progress in nanotechnology research to design and evaluate membrane-targeting virus inhibition strategies. These efforts span diverse topics such as nanomaterials, self-assembly, biosensors, nanomedicine, drug delivery, and medical devices and have excellent potential to support the development of next-generation antiviral drug candidates and technologies. Application examples in the areas of human medicine and agricultural biosecurity are also presented. Looking forward, research in this direction is poised to strengthen capabilities for virus pandemic preparedness and demonstrates how nanotechnology strategies can help to solve global health challenges related to infectious diseases.
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Affiliation(s)
- Bo Kyeong Yoon
- School of Chemical Engineering and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Won-Yong Jeon
- School of Chemical Engineering and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Tun Naw Sut
- School of Chemical Engineering and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Republic of Korea
- School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, 639798 Singapore
| | - Nam-Joon Cho
- School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, 639798 Singapore
| | - Joshua A Jackman
- School of Chemical Engineering and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Republic of Korea
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Bali P, Lozano-Pope I, Pachow C, Obonyo M. Early detection of tumor cells in bone marrow and peripheral blood in a fast‑progressing gastric cancer model. Int J Oncol 2021; 58:388-396. [PMID: 33469673 PMCID: PMC7864146 DOI: 10.3892/ijo.2021.5171] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Accepted: 10/15/2020] [Indexed: 12/13/2022] Open
Abstract
Helicobacter pylori (H. pylori) infection is a major risk factor for the development of gastric cancer. The authors previously demonstrated that in mice deficient in myeloid differentiation primary response 88 (Myd88−/−), infection with Helicobacter felis (H. felis) a close relative of H. pylori, subsequently rapidly progressed to neoplasia. The present study examined circulating tumor cells (CTCs) by measuring the expression of cytokeratins, epithelial-to-mesenchymal transition (EMT)-related markers and cancer stem cell (CSC) markers in bone marrow and peripheral blood from Myd88−/− and wild-type (WT) mice. Cytokeratins CK8/18 were detected as early as 4 months post-infection in Myd88−/− mice. By contrast, cytokeratins were not detected in WT mice even after 7 months post-infection. The expression of Mucin-1 (MUC1) was observed in both bone marrow and peripheral blood at different time points, suggesting its role in gastric cancer metastasis. Snail, Twist and ZEB were expressed at different levels in bone marrow and peripheral blood. The expression of these EMT-related markers suggests the manifestation of cancer metastasis in the early stages of disease development. LGR5, CD44 and CD133 were the most prominent CSC markers detected. The detection of CSC and EMT markers along with cytokeratins does reinforce their use as biomarkers for gastric cancer metastasis. This early detection of markers suggests that CTCs leave primary site even before cancer is well established. Thus, cytokeratins, EMT, and CSCs could be used as biomarkers to detect aggressive forms of gastric cancers. This information may prove to be of significance in stratifying patients for treatment prior to the onset of severe disease-related characteristics.
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Affiliation(s)
- Prerna Bali
- Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093‑0640, USA
| | - Ivonne Lozano-Pope
- Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093‑0640, USA
| | - Collin Pachow
- Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093‑0640, USA
| | - Marygorret Obonyo
- Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093‑0640, USA
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Wang M, Xin Y, Cao H, Li W, Hua Y, Webster TJ, Zhang C, Tang W, Liu Z. Recent advances in mesenchymal stem cell membrane-coated nanoparticles for enhanced drug delivery. Biomater Sci 2020; 9:1088-1103. [PMID: 33332490 DOI: 10.1039/d0bm01164a] [Citation(s) in RCA: 83] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Studies of nanomedicine have achieved dramatic progress in recent decades. However, the main challenges that traditional nanomedicine has to overcome include low accumulation at target sites and rapid clearance from the blood circulation. An interesting approach using cell membrane coating technology has emerged as a possible way to overcome these limitations, owing to the enhanced targeted delivery and reduced immunogenicity of cell membrane moieties. Mesenchymal stem cell (MSC) therapy has been investigated for treating various diseases, ranging from inflammatory diseases to tissue damage. Recent studies with engineered modified MSCs or MSC membranes have focused on enhancing cell therapeutic efficacy. Therefore, bioengineering strategies that couple synthetic nanoparticles with MSC membranes have recently received much attention due to their homing ability and tumor tropism. Given the various membrane receptors on their surfaces, MSC membrane-coated nanoparticles are an effective method with selective targeting properties, allowing entry into specific cells. Here, we review recent progress on the use of MSC membrane-coated nanoparticles for biomedical applications, particularly in the two main antitumor and anti-inflammatory fields. The combination of a bioengineered cell membrane and synthesized nanoparticles presents a wide range of possibilities for the further development of targeted drug delivery, showing the potential to enhance the therapeutic efficacy for treating various diseases.
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Affiliation(s)
- Mian Wang
- Department of Cardiology, Research Center for Translational Medicine, Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, School of Medicine, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
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Kermanizadeh A, Jacobsen NR, Murphy F, Powell L, Parry L, Zhang H, Møller P. A Review of the Current State of Nanomedicines for Targeting and Treatment of Cancers: Achievements and Future Challenges. ADVANCED THERAPEUTICS 2020. [DOI: 10.1002/adtp.202000186] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
| | | | - Fiona Murphy
- Heriot Watt University School of Engineering and Physical Sciences Edinburgh EH14 4AS UK
| | - Leagh Powell
- Heriot Watt University School of Engineering and Physical Sciences Edinburgh EH14 4AS UK
| | - Lee Parry
- Cardiff University European Cancer Stem Cell Research Institute, School of Biosciences Cardiff CF24 4HQ UK
| | - Haiyuan Zhang
- Changchun Institute of Applied Chemistry Laboratory of Chemical Biology Changchun 130022 China
| | - Peter Møller
- University of Copenhagen Department of Public Health Copenhagen DK1014 Denmark
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Correlations between α-Linolenic Acid-Improved Multitissue Homeostasis and Gut Microbiota in Mice Fed a High-Fat Diet. mSystems 2020; 5:5/6/e00391-20. [PMID: 33144308 PMCID: PMC7646523 DOI: 10.1128/msystems.00391-20] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Previous studies have shown that α-linolenic acid (ALA) has a significant regulatory effect on related disorders induced by high-fat diets (HFDs), but little is known regarding the correlation between the gut microbiota and disease-related multitissue homeostasis. We systematically investigated the effects of ALA on the body composition, glucose homeostasis, hyperlipidemia, metabolic endotoxemia and systemic inflammation, white adipose tissue (WAT) homeostasis, liver homeostasis, intestinal homeostasis, and gut microbiota of mice fed an HFD (HFD mice). We found that ALA improved HFD-induced multitissue metabolic disorders and gut microbiota disorders to various degrees. Importantly, we established a complex but clear network between the gut microbiota and host parameters. Several specific differential bacteria were significantly associated with improved host parameters. Rikenellaceae_RC9_gut_group and Parasutterella were positively correlated with HFD-induced "harmful indicators" and negatively correlated with "beneficial indicators." Intriguingly, Bilophila showed a strong negative correlation with HFD-induced multitissue metabolic disorders and a significant positive correlation with most beneficial indicators, which is different from its previous characterization as a "potentially harmful genus." Turicibacter might be the key beneficial bacterium for ALA-improved metabolic endotoxemia, while Blautia might play an important role in ALA-improved gut barrier integrity and anti-inflammatory effects. The results suggested that the gut microbiota, especially some specific bacteria, played an important role in the process of ALA-improved multitissue homeostasis in HFD mice, and different bacteria might have different divisions of regulation.IMPORTANCE Insufficient intake of n-3 polyunsaturated fatty acids is an important issue in modern Western-style diets. A large amount of evidence now suggests that a balanced intestinal microecology is considered an important part of health. Our results show that α-linolenic acid administration significantly improved the host metabolic phenotype and gut microbiota of mice fed a high-fat diet, and there was a correlation between the improved gut microbiota and metabolic phenotype. Some specific bacteria may play a unique regulatory role. Here, we have established correlation networks between gut microbiota and multitissue homeostasis, which may provide a new basis for further elucidating the relationship between the gut microbiota and host metabolism.
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Henriques PC, Costa LM, Seabra CL, Antunes B, Silva-Carvalho R, Junqueira-Neto S, Maia AF, Oliveira P, Magalhães A, Reis CA, Gartner F, Touati E, Gomes J, Costa P, Martins MCL, Gonçalves IC. Orally administrated chitosan microspheres bind Helicobacter pylori and decrease gastric infection in mice. Acta Biomater 2020; 114:206-220. [PMID: 32622054 DOI: 10.1016/j.actbio.2020.06.035] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 06/22/2020] [Accepted: 06/25/2020] [Indexed: 12/13/2022]
Abstract
Persistent Helicobacter pylori (H. pylori) infection is related to 90% of gastric cancers. With bacterial resistance rising and treatment inefficiency affecting 15% of the patients, alternative treatments urge. Chitosan microspheres (ChMics) have been proposed as an H. pylori-binding system. This work evaluates ChMics biocompatibility, mucopenetration and capacity to treat H. pylori infection in mice after oral administration. ChMics of different size (XL, ∼120 µm and XS, ∼40 µm) and degree of acetylation (6% and 16%) were developed and revealed to be able to adhere both human and mouse-adapted H. pylori strains without cytotoxicity towards human gastric cells. Ex vivo studies showed that smaller (XS) microspheres penetrate further within the gastric foveolae, suggesting their ability to reach deeply adherent bacteria. In vivo assays showed 88% reduction of infection when H. pylori-infected mice (C57BL/6) were treated with more mucoadhesive XL6 and XS6 ChMics. Overall, ChMics clearly demonstrate ability to reduce H. pylori gastric infection in mice, with chitosan degree of acetylation being a dominant factor over microspheres' size on H. pylori removal efficiency. These results evidence the strong potential of this strategy as an antibiotic-free approach to fight H. pylori infection, where microspheres are orally administered, bind H. pylori in the stomach, and remove them through the gastrointestinal tract. STATEMENT OF SIGNIFICANCE: Approximately 90% of gastric cancers are caused by the carcinogenic agent Helicobacter pylori, which infects >50% of the world population. Bacterial resistance, reduced antibiotic bioavailability, and the intricate distribution of bacteria in mucus and within gastric foveolae hamper the success of most strategies to fight H. pylori. We demonstrate that an antibiotic-free therapy based on bare chitosan microspheres that bind and remove H. pylori from stomach can achieve 88% reduction of infection from H. pylori-infected mice. Changing size and mucoadhesive properties, microspheres can reach different areas of gastric mucosa: smaller and less mucoadhesive can penetrate deeper into the foveolae. This promising, simple and inexpensive strategy paves the way for a faster bench-to-bedside transition, therefore holding great potential for clinical application.
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Affiliation(s)
- Patrícia C Henriques
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
| | - Lia M Costa
- INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
| | - Catarina L Seabra
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal
| | - Bernardo Antunes
- INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
| | - Ricardo Silva-Carvalho
- INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
| | - Susana Junqueira-Neto
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal
| | - André F Maia
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
| | - Pedro Oliveira
- ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
| | - Ana Magalhães
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal
| | - Celso A Reis
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal; Faculdade de Medicina, Universidade do Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
| | - Fátima Gartner
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
| | - Eliette Touati
- Unit of Helicobacter Pathogenesis, Department of Microbiology, CNRS UMR2001, Institut Pasteur, 25-28 Rue du Dr. Roux, 75015, Paris, France
| | - Joana Gomes
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal
| | - Paulo Costa
- UCIBIO/REQUIMTE, MedTech-Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4150-755 Porto, Portugal
| | - M Cristina L Martins
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
| | - Inês C Gonçalves
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal.
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Enrofloxacin Shifts Intestinal Microbiota and Metabolic Profiling and Hinders Recovery from Salmonella enterica subsp. enterica Serovar Typhimurium Infection in Neonatal Chickens. mSphere 2020; 5:5/5/e00725-20. [PMID: 32907952 PMCID: PMC7485687 DOI: 10.1128/msphere.00725-20] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Enrofloxacin is an important antibiotic used for prevention and treatment of Salmonella infection in poultry in many countries. However, oral administration of enrofloxacin may lead to the alterations in the microbiota and metabolome in the chicken intestine, thereby reducing colonization resistance to the Salmonella infection. To study the effect of enrofloxacin on Salmonella in the chicken cecum, we used different concentrations of enrofloxacin to feed 1-day-old chickens, followed by oral challenge with Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium). We then explored the distribution pattern of S. Typhimurium in cecum contents in vivo and analyzed the microbial community structure of cecum contents using microbial 16S amplicon sequencing. Untargeted metabolomics was used to explore the gut metabolome on day 14. Faecalibacterium and Anaerostipes, which are closely related to the chicken intestinal metabolome, were screened using a multi-omics technique. The abundance of S. Typhimurium was significantly higher in the enrofloxacin-treated group than in the untreated group, and S. Typhimurium persisted longer. Moreover, the cecal colony structures of the three groups exhibited different characteristics, with Lactobacillus reaching its highest abundance on day 21. Notably, S. Typhimurium infection is known to affect the fecal metabolome of chickens differently. Thus, our results suggested that enrofloxacin and Salmonella infections completely altered the intestinal microbiota and metabolism of chickens.IMPORTANCE In this study, we examined the effects of S. Typhimurium infection and enrofloxacin treatment on the microbiota and metabolite synthesis in chicken cecum, in order to identify target metabolites that may promote S. Typhimurium colonization and aggravate inflammation and to evaluate the important microbiota that may be associated with these metabolites. Our findings may facilitate the use of antibiotics to prevent S. Typhimurium infection.
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Bacterial outer membrane vesicles as a platform for biomedical applications: An update. J Control Release 2020; 323:253-268. [PMID: 32333919 DOI: 10.1016/j.jconrel.2020.04.031] [Citation(s) in RCA: 200] [Impact Index Per Article: 40.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2019] [Revised: 04/02/2020] [Accepted: 04/20/2020] [Indexed: 12/11/2022]
Abstract
Outer membrane vesicles (OMVs) are produced by Gram-negative bacteria both in vitro and in vivo. OMVs are nano-sized spherical vehicles formed by lipid bilayer membranes and contain multiple parent bacteria-derived components. Based on the presence of bacterial antigens, pathogen-associated molecular patterns (PAMPs), adhesins, various proteins and the vesicle structure, OMVs have been developed for biomedical applications as bacterial vaccines, adjuvants, cancer immunotherapy agents, drug delivery vehicles, and anti-bacteria adhesion agents. In this review, we analyze the contributions of the structure and composition of OMVs to their applications, summarize the methods used to isolate and characterize OMVs, and highlight recent progress and future perspectives of OMVs in biomedical applications.
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Jiménez-Avalos JA, Arrevillaga-Boni G, González-López L, García-Carvajal ZY, González-Avila M. Classical methods and perspectives for manipulating the human gut microbial ecosystem. Crit Rev Food Sci Nutr 2020; 61:234-258. [PMID: 32114770 DOI: 10.1080/10408398.2020.1724075] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
A healthy Human Gut Microbial Ecosystem (HGME) is a necessary condition for maintaining the orderly function of the whole body. Major alterations in the normal gut microbial composition, activity and functionality (dysbiosis) by an environmental or host-related disruptive event, can compromise metabolic, inflammatory, and neurological processes, causing disorders such as obesity, inflammatory bowel disease, colorectal cancer, and depressive episodes. The restore or the maintaining of the homeostatic balance of Gut Microbiota (GM) populations (eubiosis) is possible through diet, the use of probiotics, prebiotics, antibiotics, and even Fecal Microbiota Transplantation (FMT). Although these "classic methods" represent an effective and accepted way to modulate GM, the complexity of HGME requires new approaches to control it in a more appropriate way. Among the most promising emergent strategies for modulating GM are the use of engineered nanomaterials (metallic nanoparticles (NP), polymeric-NP, quantum dots, micelles, dendrimers, and liposomes); phagotherapy (i.e., phages linked with the CRISPR/Cas9 system), and the use of antimicrobial peptides, non-antibiotic drugs, vaccines, and immunoglobulins. Here we review the current state of development, implications, advantages, disadvantages, and perspectives of the different approaches for manipulating HGME.
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Affiliation(s)
- Jorge Armando Jiménez-Avalos
- Medical and Pharmaceutical Biotechnology Department, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ), Guadalajara, Jalisco, Mexico
| | - Gerardo Arrevillaga-Boni
- Medical and Pharmaceutical Biotechnology Department, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ), Guadalajara, Jalisco, Mexico
| | | | - Zaira Yunuen García-Carvajal
- Medical and Pharmaceutical Biotechnology Department, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ), Guadalajara, Jalisco, Mexico
| | - Marisela González-Avila
- Medical and Pharmaceutical Biotechnology Department, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ), Guadalajara, Jalisco, Mexico
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Zhang Q, Wu W, Zhang J, Xia X. Eradication of Helicobacter pylori: the power of nanosized formulations. Nanomedicine (Lond) 2020; 15:527-542. [PMID: 32028847 DOI: 10.2217/nnm-2019-0329] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori is a pathogen that is considered to cause several gastric disorders such as chronic gastritis, peptic ulcer and even gastric carcinoma. The current therapeutic regimens mainly constitute of a combination of several antimicrobial agents and proton pump inhibitors. However, the prevalence of antibiotic resistance has been significantly lowering the cure rates over the years. Nanocarriers possess unique strengths in this regard owing to the fact that they can protect the drugs (such as antibiotics) from the harsh environment in the stomach, penetrate the mucosal barrier and deliver drugs to the desired site. In this review we summarized recent studies of different antibacterial agents orally delivered by nanosized carriers for the eradication of H. pylori.
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Affiliation(s)
- Qianyu Zhang
- Innovative Drug Research Center (IDRC), School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331, PR China
| | - Wen Wu
- Innovative Drug Research Center (IDRC), School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331, PR China
| | - Jinqiang Zhang
- Innovative Drug Research Center (IDRC), School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331, PR China
| | - Xuefeng Xia
- Innovative Drug Research Center (IDRC), School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331, PR China
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Jiang M, Ma L, Huang Y, Wu H, Dou J, Zhou C. Antimicrobial activities of peptide Cbf-K 16 against drug-resistant Helicobacter pylori infection in vitro and in vivo. Microb Pathog 2019; 138:103847. [PMID: 31704464 DOI: 10.1016/j.micpath.2019.103847] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Revised: 10/25/2019] [Accepted: 11/04/2019] [Indexed: 02/08/2023]
Abstract
Helicobacter pylori (H. pylori) infection is highly prevalent, and has developed antimicrobial resistance to virtually all existing antibiotics. Currently, treatment of H. pylori infection (involving proton pump inhibitors and broad-spectrum antibiotics) is suboptimal, with high failure rates. Thus, there is a pressing need to develop new anti-H. pylori therapies. Cbf-K16, a cathelicidin-like antimicrobial peptide, presented broad antimicrobial activity during our previous research. This study further evaluated the therapeutic potential and the mode of action underlying Cbf-K16 against clarithromycin- and amoxicillin-resistant H. pylori SS1. The MIC and MBC of Cbf-K16 against the tested H. pylori were 16 and 32 μg/ml, respectively, and its killing kinetics was time-dependent, reflecting the thorough elimination of drug-resistant bacteria within 24 h. This peptide also protected H. pylori-infected gastric epithelial cells (GES-1) from death by reducing the cell supernatant and intracellular bacterial counts by 1.9 and 2.9-log10 units, respectively. These data indicated the powerful antimicrobial effects of Cbf-K16in vitro. Meanwhile, notable antimicrobial activity in the mouse gastritis model was observed, with decreasing bacterial counts by 3.9-log10 units in stomach tissues and Cbf-K16 could effectively suppress the secretion of inflammatory cytokine IL-8. For its mode of action, Cbf-K16 not only neutralized the negative potential and increased the membrane uptake of NPN and PI by 78.5% and 85.1%, respectively, but also bound to genomic DNA, which in turn downregulated the expression of adhesion genes (alpA and alpB) and virulence gene (cagA), indicating its effective activities on membrane disruption, DNA-binding and gene expression. The data above demonstrated that Cbf-K16 possessed effective antimicrobial and anti-inflammatory activities and downregulated the expression of adhesion- and cytotoxin-associated genes of drug-resistant H. pylori SS1, making it a potential candidate for anti-infective therapy.
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Affiliation(s)
- Meiling Jiang
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu, 210009, PR China
| | - Lingman Ma
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu, 210009, PR China
| | - Ya Huang
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu, 210009, PR China
| | - Haomin Wu
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu, 210009, PR China
| | - Jie Dou
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu, 210009, PR China
| | - Changlin Zhou
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu, 210009, PR China.
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