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Wang H, Zhang W, Sun Y, Xu X, Chen X, Zhao K, Yang Z, Liu H. Nanotherapeutic strategies exploiting biological traits of cancer stem cells. Bioact Mater 2025; 50:61-94. [PMID: 40242505 PMCID: PMC12002948 DOI: 10.1016/j.bioactmat.2025.03.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Revised: 03/08/2025] [Accepted: 03/20/2025] [Indexed: 04/18/2025] Open
Abstract
Cancer stem cells (CSCs) represent a distinct subpopulation of cancer cells that orchestrate cancer initiation, progression, metastasis, and therapeutic resistance. Despite advances in conventional therapies, the persistence of CSCs remains a major obstacle to achieving cancer eradication. Nanomedicine-based approaches have emerged for precise CSC targeting and elimination, offering unique advantages in overcoming the limitations of traditional treatments. This review systematically analyzes recent developments in nanomedicine for CSC-targeted therapy, emphasizing innovative nanomaterial designs addressing CSC-specific challenges. We first provide a detailed examination of CSC biology, focusing on their surface markers, signaling networks, microenvironmental interactions, and metabolic signatures. On this basis, we critically evaluate cutting-edge nanomaterial engineering designed to exploit these CSC traits, including stimuli-responsive nanodrugs, nanocarriers for drug delivery, and multifunctional nanoplatforms capable of generating localized hyperthermia or reactive oxygen species. These sophisticated nanotherapeutic approaches enhance selectivity and efficacy in CSC elimination, potentially circumventing drug resistance and cancer recurrence. Finally, we present an in-depth analysis of current challenges in translating nanomedicine-based CSC-targeted therapies from bench to bedside, offering critical insights into future research directions and clinical implementation. This review aims to provide a comprehensive framework for understanding the intersection of nanomedicine and CSC biology, contributing to more effective cancer treatment modalities.
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Affiliation(s)
- Hongyu Wang
- State Key Laboratory of Organic-Inorganic Composites, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing Key Laboratory of Bioprocess, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, 100029, Beijing, China
| | - Wenjing Zhang
- State Key Laboratory of Green Biomanufacturing, Innovation Center of Molecular Diagnostics, College of Life Science and Technology, Beijing University of Chemical Technology, 100029, Beijing, China
| | - Yun Sun
- State Key Laboratory of Organic-Inorganic Composites, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing Key Laboratory of Bioprocess, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, 100029, Beijing, China
| | - Xican Xu
- State Key Laboratory of Organic-Inorganic Composites, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing Key Laboratory of Bioprocess, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, 100029, Beijing, China
| | - Xiaoyang Chen
- State Key Laboratory of Green Biomanufacturing, Innovation Center of Molecular Diagnostics, College of Life Science and Technology, Beijing University of Chemical Technology, 100029, Beijing, China
| | - Kexu Zhao
- State Key Laboratory of Green Biomanufacturing, Innovation Center of Molecular Diagnostics, College of Life Science and Technology, Beijing University of Chemical Technology, 100029, Beijing, China
| | - Zhao Yang
- State Key Laboratory of Green Biomanufacturing, Innovation Center of Molecular Diagnostics, College of Life Science and Technology, Beijing University of Chemical Technology, 100029, Beijing, China
| | - Huiyu Liu
- State Key Laboratory of Organic-Inorganic Composites, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing Key Laboratory of Bioprocess, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, 100029, Beijing, China
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2
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Bolideei M, Barzigar R, Gahrouei RB, Mohebbi E, Haider KH, Paul S, Paul MK, Mehran MJ. Applications of Gene Editing and Nanotechnology in Stem Cell-Based Therapies for Human Diseases. Stem Cell Rev Rep 2025; 21:905-934. [PMID: 40014250 DOI: 10.1007/s12015-025-10857-0] [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] [Accepted: 02/23/2025] [Indexed: 02/28/2025]
Abstract
Stem cell research is a dynamic and fast-advancing discipline with great promise for the treatment of diverse human disorders. The incorporation of gene editing technologies, including ZFNs, TALENs, and the CRISPR/Cas system, in conjunction with progress in nanotechnology, is fundamentally transforming stem cell therapy and research. These innovations not only provide a glimmer of optimism for patients and healthcare practitioners but also possess the capacity to radically reshape medical treatment paradigms. Gene editing and nanotechnology synergistically enhance stem cell-based therapies' precision, efficiency, and applicability, offering transformative potential for treating complex diseases and advancing regenerative medicine. Nevertheless, it is important to acknowledge that these technologies also give rise to ethical considerations and possible hazards, such as inadvertent genetic modifications and the development of genetically modified organisms, therefore creating a new age of designer infants. This review emphasizes the crucial significance of gene editing technologies and nanotechnology in the progress of stem cell treatments, particularly for degenerative pathologies and injuries. It emphasizes their capacity to restructure and comprehensively revolutionize medical treatment paradigms, providing fresh hope and optimism for patients and healthcare practitioners.
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Affiliation(s)
- Mansoor Bolideei
- Department of Respiratory and Critical Care Medicine, the Center for Biomedical Research, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China
| | - Rambod Barzigar
- Department of Biotechnology, SJCE Technical Campus, JSS Research Foundation, University of Mysore, Mysore, 570006, Karnataka, India
| | - Razieh Bahrami Gahrouei
- Department of Pharmacy PES College, Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka, India
| | - Elham Mohebbi
- Department of Medical Microbiology, Immunology, and Cell Biology, Southern Illinois School of Medicine, Springfield, IL, USA
| | - Khawaja Husnain Haider
- Sulaiman AlRajhi Medical School, Al Bukayriyah, AlQaseem, 52726, Kingdom of Saudi Arabia
| | - Sayan Paul
- Department of Biochemistry & Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, TX, 77555, USA.
| | - Manash K Paul
- Department of Radiation Biology and Toxicology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
| | - Mohammad Javad Mehran
- Department of Biotechnology, SJCE Technical Campus, JSS Research Foundation, University of Mysore, Mysore, 570006, Karnataka, India.
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Cai L, Yang Q, Shao X, Wang S, Fu Y, Mao X, Hou L, Meng Y, Wei Y, Xu X. Dual-responsive triple-helix β-glucan-based self-assembled supramolecule for combination chemo-photothermal therapy against lung metastatic triple negative breast cancer. Int J Biol Macromol 2025; 306:141370. [PMID: 39988177 DOI: 10.1016/j.ijbiomac.2025.141370] [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: 12/13/2024] [Revised: 02/16/2025] [Accepted: 02/20/2025] [Indexed: 02/25/2025]
Abstract
The development of multifunctional therapies with targeted release materials is desirable for overcoming the high aggressiveness and poor prognosis of triple-negative breast cancer (TNBC). Herein, we have designed a self-assembled supramolecule (BSD), in which SWNTs can be wrapped by triple-helix β-Glucan (BFP) in a self-assembled manner, and doxorubicin (DOX) is attached onto SWNTs by means of π-stacking and hydrophobic interactions with high drug encapsulation efficiency (89.3 %). BFP could significantly improve the dispersion and stability of SWNTs and DOX, and reduce toxicity. BSD provides a drug-targeting mechanism due to the pH-responsive and near-infrared radiation (NIR) thermal-responsive release of DOX, and BSD displayed excellent photo-thermal conversion effect and cyclic stability, and exhibited higher antitumor activity under near-infrared radiation than chemotherapy alone. Photothermal therapy mainly blocked the synthesis of nutrients required for tumor DNA replication, while chemotherapy markedly induced oxidative stress production, which ultimately exacerbated DNA damage of tumor cells. As a result, the combined effect of chemo-photothermal therapy ultimately promote tumor cell apoptosis and suppress the growth of primary tumor and metastasis to the lungs in vitro and in vivo. This study provides a promising pH/NIR thermal-responsive sustained prodrug for combined chemo-photothermal therapy against aggressive triple negative breast cancer in practical therapy.
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Affiliation(s)
- Liqin Cai
- School of Advanced Manufacturing, College of Chemical Engineering, Fuzhou University, Fuzhou, Fujian 350116, China; College of Chemistry and Molecular Sciences, Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei 430072, China.
| | - Qian Yang
- College of Chemistry and Molecular Sciences, Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei 430072, China
| | - Xiang Shao
- School of Advanced Manufacturing, College of Chemical Engineering, Fuzhou University, Fuzhou, Fujian 350116, China
| | - Sen Wang
- School of Advanced Manufacturing, College of Chemical Engineering, Fuzhou University, Fuzhou, Fujian 350116, China
| | - Yaming Fu
- School of Advanced Manufacturing, College of Chemical Engineering, Fuzhou University, Fuzhou, Fujian 350116, China
| | - Xinghuai Mao
- School of Advanced Manufacturing, College of Chemical Engineering, Fuzhou University, Fuzhou, Fujian 350116, China
| | - Linxi Hou
- School of Advanced Manufacturing, College of Chemical Engineering, Fuzhou University, Fuzhou, Fujian 350116, China
| | - Yan Meng
- College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China
| | - Yongchang Wei
- College of Chemistry and Molecular Sciences, Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei 430072, China.
| | - Xiaojuan Xu
- College of Chemistry and Molecular Sciences, Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei 430072, China.
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Liu D, Zhang Q, Wang L, Wang R, Zhu W, Xing G, Wang J, Zhang Q, Cai D. Targeting the CD44 receptor with hyaluronic acid-modified SWCNTs for 17-hydroxy-jolkinolide B delivery to inhibit breast cancer metastasis. Int J Biol Macromol 2025; 310:143260. [PMID: 40250688 DOI: 10.1016/j.ijbiomac.2025.143260] [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: 12/12/2024] [Revised: 03/28/2025] [Accepted: 04/15/2025] [Indexed: 04/20/2025]
Abstract
17-Hydroxy-jolkinolide B (HJB), an active ingredient extract from Euphorbia fischeriana Steud., has attracted much attention due to its high efficiency and low toxicity in cancer treatment. However, its clinical potential is compromised by low bioavailability and poor tumor targeting. We developed hyaluronic acid (HA) modified single-walled carbon nanotubes (SWCNTs) for CD44 receptor-mediated targeted delivery of HJB to enhance tumor targeting and therapeutic efficacy. The generated HA-SWCNTs-HJB measured 363.9 ± 12.8 nm in size with a HJB encapsulation efficiency of 61.5 %. HA-SWCNTs-Cou6 was effectively internalized into 4 T1 cells by receptor-mediated endocytosis, exhibiting a 4.23-fold increase compared to passive targeting SWCNTs-Cou6. Moreover, HA-SWCNTs-HJB exhibited higher cytotoxicity against 4 T1 cells than SWCNTs-HJB. The IC50 values at 48 h were 3.9 ± 0.5 and 5.7 ± 0.5 μM, respectively. In vivo fluorescence imaging revealed enhanced tumor accumulation in 4 T1 breast cancer-bearing mice due to CD44 receptor-mediated active targeting. Additionally, HA-SWCNTs-HJB significantly inhibited the tumor growth and suppressed breast cancer metastasis without noticeable side effects in vivo. Overall, our newly developed HJB delivery system HA-SWCNTs-HJB, may be a potential therapeutic strategy for effectively treating breast cancer growth and metastasis.
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Affiliation(s)
- Dan Liu
- Institute of Medicine and Drug Research, Qiqihar Medical University, Qiqihar, PR China.
| | - Qiyue Zhang
- Institute of Medicine and Drug Research, Qiqihar Medical University, Qiqihar, PR China
| | - Liang Wang
- Institute of Medicine and Drug Research, Qiqihar Medical University, Qiqihar, PR China.
| | - Rui Wang
- Institute of Medicine and Drug Research, Qiqihar Medical University, Qiqihar, PR China
| | - Wenquan Zhu
- College of Pharmacy, Qiqihar Medical University, Qiqihar, PR China.
| | - Guihua Xing
- College of Pathology, Qiqihar Medical University, Qiqihar, PR China.
| | - Jing Wang
- Institute of Medicine and Drug Research, Qiqihar Medical University, Qiqihar, PR China.
| | - Qi Zhang
- Institute of Medicine and Drug Research, Qiqihar Medical University, Qiqihar, PR China.
| | - Defu Cai
- Institute of Medicine and Drug Research, Qiqihar Medical University, Qiqihar, PR China.
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Sundaram P, Dhilip Kumar SS, Abrahamse H. Targeted Delivery of Chlorin-e6-Loaded Carbon Nanotube-Based Nanobiocomposite to Cancer Stem Cells for Enhanced Photodynamic Therapy. Pharmaceutics 2025; 17:469. [PMID: 40284464 PMCID: PMC12030014 DOI: 10.3390/pharmaceutics17040469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2025] [Revised: 03/24/2025] [Accepted: 03/27/2025] [Indexed: 04/29/2025] Open
Abstract
Background: Globally, colorectal cancer (CRC) is the third-most diagnosed cancer among males and the second-most diagnosed cancer among females. In cancer, stem cells are a subset of neoplastic cells capable of tumorigenesis and exhibit properties like normal stem cells. Moreover, they are resistant to conventional cancer treatments and can repopulate the tumor following treatment. Cancer cells are stimulated to undergo apoptosis by photodynamic therapy (PDT), which involves a light source, a photosensitizer, and reactive oxygen species. Methods: In this study, colon cancer stem cells were isolated from colon cancer cells and characterized using flow cytometry and immunofluorescence techniques. To treat colon cancer stem cells (CCSCs), single-walled carbon nanotubes (SWCNTs) were coupled with hyaluronic acid (HA) and loaded with chlorin-e6 (Ce6). Nanobiocomposite toxicity was assessed using CCSCs with two fluences of 5 J/cm2 and 10 J/cm2. The cellular changes were observed at 24 and 48 h using microscopy, Results: LDH cytotoxicity assay, and cell death induction by annexin propidium iodide assay. An intracellular analysis of reactive oxygen species (ROS) detected oxidative stress within CCSCs. Conclusions: Overall, the results showed that the newly synthesized nanobiocomposite enhanced the ability of PDT to act as a photosensitizer carrier and induced cell death in CCSCs.
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Affiliation(s)
| | | | - Heidi Abrahamse
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Johannesburg 2028, South Africa; (P.S.); (S.S.D.K.)
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Matysiak-Kucharek M, Sawicki K, Kruszewski M, Kurzepa J, Kapka-Skrzypczak L. Prometastatic Potential of Non-Functionalized Multiwalled Carbon Nanotubes in the MDA-MB-436 Breast Cancer Cell Line Model. Int J Mol Sci 2025; 26:2777. [PMID: 40141419 PMCID: PMC11943048 DOI: 10.3390/ijms26062777] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Revised: 03/14/2025] [Accepted: 03/17/2025] [Indexed: 03/28/2025] Open
Abstract
Multiwalled carbon nanotubes (MWCNTs) are used in many areas of industry and medicine. However, there is evidence suggesting profibrogenic action of MWCNTs, probably via the epithelial-mesenchymal transition mechanism (EMT). The aim of this study was to evaluate the prometastatic activity of 5-20 nm and 50-80 nm MWCNTs against cells of the MDA-MB-436 line. We used MTT and NR assays to determine MWCNTs' cytotoxicity and the level of malonylodialdehyde and thiol compounds as indicators of oxidative stress. qRT-PCR was used to examine the expression of EMT markers. The QCM Chemotaxis Cell Migration Assay was used to assess cell migration, while the Cytokine Array Kit and Apoptosis Array Kit were used to determine cytokine expression and induction of apoptosis. The interleukin 6, C-X-C motif chemokine ligand 8, and tumor growth factor beta 1 (TGFB1) secretion was determined by ELISA. MWCNTs were toxic to MDA-MB-436 cells and induced cell death via the apoptosis pathway. MWCNTs induced a low level of oxidative stress and were associated with increased secretion of pro-inflammatory cytokines and chemokines, including proteins important in breast cancer metastasis. Cells incubated with MWCNTs showed increased expression of mesenchymal EMT markers. However, in contrast to these results, the migration of MWCNT-treated cells increased only modestly relative to untreated cells. Also, the secretion of TGFB1, a key inducer and regulator of EMT, increased only slightly. In summary, the multifaceted effect of MWCNTs on cancer cells encourages further work on the safety of nanomaterials.
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Affiliation(s)
- Magdalena Matysiak-Kucharek
- Department of Molecular Biology and Translational Research, Institute of Rural Health, 20-090 Lublin, Poland; (M.M.-K.); (K.S.)
| | - Krzysztof Sawicki
- Department of Molecular Biology and Translational Research, Institute of Rural Health, 20-090 Lublin, Poland; (M.M.-K.); (K.S.)
| | - Marcin Kruszewski
- Center for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, 03-195 Warsaw, Poland;
| | - Jacek Kurzepa
- Department of Medical Chemistry, Medical University of Lublin, 20-093 Lublin, Poland;
| | - Lucyna Kapka-Skrzypczak
- Department of Molecular Biology and Translational Research, Institute of Rural Health, 20-090 Lublin, Poland; (M.M.-K.); (K.S.)
- World Institute for Family Health, Calisia University, 62-800 Kalisz, Poland
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7
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Yang T, Guo L. Advancing gastric cancer treatment: nanotechnology innovations and future prospects. Cell Biol Toxicol 2024; 40:101. [PMID: 39565472 PMCID: PMC11579161 DOI: 10.1007/s10565-024-09943-9] [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: 06/24/2024] [Accepted: 11/04/2024] [Indexed: 11/21/2024]
Abstract
Gastric cancer (GC) is the fifth most common cancer worldwide, particularly prevalent in Asia, especially in China, where both its incidence and mortality rates are significantly high. Meanwhile, nanotechnology has demonstrated great potential in the treatment of GC. In particular, nanodrug delivery systems have improved therapeutic efficacy and targeting through various functional modifications, such as targeting peptides, tumor microenvironment responsiveness, and instrument-based methods. For instance, silica (SiO2) has excellent biocompatibility and can be used as a drug carrier, with its porous structure enhancing drug loading capacity. Polymer nanoparticles regulate drug release rates and mechanisms by altering material composition and preparation methods. Lipid nanoparticles efficiently encapsulate hydrophilic drugs and promote cellular uptake, while carbon-based nanoparticles can be used in biosensors and drug delivery. Targets such as integrins, HER2 receptors, and the tumor microenvironment have been used to improve drug efficacy in GC treatment. Nanodrug delivery techniques not only enhance drug efficacy and delivery capabilities but also selectively target tumor cells. Currently, there is a lack of systematic summarization and synthesis regarding the relationship between nanodrug delivery systems and GC treatment, which to some extent hinders researchers and clinicians from efficiently searching for and referencing related studies, thereby reducing work efficiency. This study aims to systematically summarize the existing research on the relationship between nanodrug delivery systems and GC treatment, making it easier for professionals to search and reference, and thereby promoting further research on the role of nanodrug delivery systems and their clinical applications in GC. This review discusses the applications of functionalized nanocarriers in the treatment of GC in recent years, including surface modifications with targeted markers, the combination of phototherapy, chemotherapy, and immunotherapy, along with their advantages and challenges. It also examines the future prospects of targeted nanomaterials in GC treatment. The review particularly focuses on the combined application of nanocarriers in multiple treatment modalities, such as phototherapy, chemotherapy, and immunotherapy, demonstrating their potential in multimodal treatments. Furthermore, it thoroughly explores the specific challenges that nanocarriers face in GC treatment, such as biocompatibility, drug release control, and clinical translation issues, while providing a systematic outlook on future developments. Additionally, this study emphasizes the potential value and feasibility of nanocarriers in clinical applications, contrasting with most reviews that focus on basic research. Through these innovations, we offer new perspectives and directions for the development of nanotechnology in the treatment of GC.
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Affiliation(s)
- Tengfei Yang
- Department of Health Management, Shengjing Hospital of China Medical University, Shenyang, 110004, P. R. China
| | - Lin Guo
- Department of General Surgery, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning Province, P. R. China.
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8
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Li F, Li Z, Wei C, Xu L, Liang Y, Yan J, Li Y, He B, Sun C. Application of hydrogels for targeting cancer stem cells in cancer treatment. Biomed Pharmacother 2024; 180:117486. [PMID: 39321506 DOI: 10.1016/j.biopha.2024.117486] [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: 06/29/2024] [Revised: 08/28/2024] [Accepted: 09/20/2024] [Indexed: 09/27/2024] Open
Abstract
Cancer stem cells (CSCs) are a major hindrance to clinical cancer treatment. Owing to their high tumorigenic and metastatic potential, CSCs are vital in malignant tumor initiation, growth, metastasis, and therapeutic resistance, leading to tumorigenesis and recurrence. Compared with normal tumor cells, CSCs express high levels of surface markers (CD44, CD90, CD133, etc.) and activate specific signaling pathways (Wnt/β-catenin, Notch, and Hedgehog). Although Current drug delivery systems (DDS) precisely target CSCs, the heterogeneity and multidrug resistance of CSCs impede CSC isolation and screening. Conversely, hydrogel DDSs exhibit good biocompatibility and high drug delivery efficiency. Hydrogels are three-dimensional (3D) spatial structures for drug encapsulation that facilitate the controlled release of bioactive molecules. Hence, hydrogels can be loaded with drugs to precisely target CSCs. Their 3D structure can also culture non-CSCs and facilitate their transformation into CSCs. for identification and isolation. Given that their elastic modulus and stiffness characteristics reflect those of the cellular microenvironment, hydrogels can simulate extracellular matrix pathways and markers to regulate CSCs, disrupting the equilibrium between CSC and non-CSC transformation. This article reviews the CSC microenvironment, metabolism, signaling pathway, and surface markers. Additionally, we summarize the existing CSC targeting strategies and explore the application of hydrogels for CSC screening and treatment. Finally, we discuss potential advances in CSC research that may lead to curative measures for tumors through targeted and precise attacks on CSCs.
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Affiliation(s)
- Fashun Li
- Department of Spinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, China; Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 266073, China
| | - Zhipeng Li
- Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 266073, China
| | - Chen Wei
- Department of Pharmacy, Qingdao Women and Children's Hospital, Qingdao 266034, China
| | - Long Xu
- School of Materials Science and Chemical Engineering, Ningbo University, Ningbo 315211, China.
| | - Yan Liang
- Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 266073, China.
| | - Jianqin Yan
- Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 266073, China
| | - Yifei Li
- Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 266073, China
| | - Bin He
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China
| | - Chong Sun
- Department of Spinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
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Amanat MA, Farrukh A, Ishaq MUBM, Bin Shafqat B, Haidri SH, Amin R, Sameen R, Kamal T, Riaz MN, Quresh W, Ikram R, Ali GM, Begum S, Bangash SAK, Kaleem I, Bashir S, Khattak SH. The Potential of Nanotechnology to Replace Cancer Stem Cells. Curr Stem Cell Res Ther 2024; 19:820-831. [PMID: 37264662 DOI: 10.2174/1574888x18666230601140700] [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: 08/21/2022] [Revised: 12/19/2022] [Accepted: 12/29/2022] [Indexed: 06/03/2023]
Abstract
Stem cells, which were initially identified in the 1900s, are distinct cells with the potential to replenish themselves as well as differentiate into specialised cells with certain forms and functions. Cancer stem cells play a significant role in the growth and recurrence of the tumours and, similar to normal stem cells, are capable of proliferating and differentiating. Traditional cancer treatments are ineffective against cancer stem cells, which leads to tumour regrowth. Cancer stem cells are thought to emerge as a result of epithelial-to-mesenchymal transition pathways. Brain, prostate, pancreatic, blood, ovarian, lung, liver, melanomas, AML, and breast cancer stem cells are among the most prevalent cancer forms. This review aims to comprehend the possibility of using specific forms of nanotechnology to replace cancer stem cells. In terms of nanotechnology, magnetic nanoparticles can deliver medications, especially to the target region without harming healthy cells, and they are biocompatible. In order to kill glioma cancer stem cells, the gold nanoparticles bond with DNA and function as radio sensitizers. In contrast, liposomes can circulate and traverse biological membranes and exhibit high therapeutic efficacy, precise targeting, and better drug release. Similar to carbon nanotubes, grapheme, and grapheme oxide, these substances can be delivered specifically when utilized in photothermal therapy. Recent treatments including signaling pathways and indicators targeted by nanoparticles are being researched. Future research in nanotechnology aims to develop more effective and targeted medicinal approaches. The results of the current investigation also showed that this technology's utilization will improve medical therapy and treatment.
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Affiliation(s)
- Muhammad Ammar Amanat
- Department of Biochemistry and Biotechnology, Faculty of Science, University of Gujrat, Gujrat Pakistan
| | | | | | - Binyameen Bin Shafqat
- Department of Biochemistry and Biotechnology, Faculty of Science, University of Gujrat, Gujrat Pakistan
| | - Saqib Hussain Haidri
- Department of Biochemistry and Biotechnology, Faculty of Science, University of Gujrat, Gujrat Pakistan
| | - Rehab Amin
- Department of Biochemistry and Biotechnology, Faculty of Science, University of Gujrat, Gujrat Pakistan
| | - Rafia Sameen
- Department of Biochemistry and Biotechnology, Faculty of Science, University of Gujrat, Gujrat Pakistan
| | - Tahira Kamal
- National Institute for Genomics and Advanced Biotechnology (NIGAB), National Agriculture Research Centre, Islamabad, Pakistan
| | - Muhammad Naeem Riaz
- National Institute for Genomics and Advanced Biotechnology (NIGAB), National Agriculture Research Centre, Islamabad, Pakistan
- Animal biotechnology program, Animal Sciences Institute (ASI), National Agriculture Research Centre (NARC), Islamabad, Pakistan
| | - Waleed Quresh
- National Institute for Genomics and Advanced Biotechnology (NIGAB), National Agriculture Research Centre, Islamabad, Pakistan
| | - Rabia Ikram
- National Institute for Genomics and Advanced Biotechnology (NIGAB), National Agriculture Research Centre, Islamabad, Pakistan
| | - Ghulam Muhammad Ali
- National Institute for Genomics and Advanced Biotechnology (NIGAB), National Agriculture Research Centre, Islamabad, Pakistan
| | - Sania Begum
- National Institute for Genomics and Advanced Biotechnology (NIGAB), National Agriculture Research Centre, Islamabad, Pakistan
| | | | - Imdad Kaleem
- Department of Biosciences, COMSATS University Islamabad, Pakistan
| | - Shahid Bashir
- Neurosciences Center, King Fahad Specialist Hospital Dammam, P.O. Box 15215, Dammam 31444, Saudi Arabia
| | - Sahir Hameed Khattak
- National Institute for Genomics and Advanced Biotechnology (NIGAB), National Agriculture Research Centre, Islamabad, Pakistan
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Lv L, Shi Y, Deng Z, Xu J, Ye Z, He J, Chen G, Yu X, Wu J, Huang X, Li G. A polymeric nanocarrier that eradicates breast cancer stem cells and delivers chemotherapeutic drugs. Biomater Res 2023; 27:133. [PMID: 38102651 PMCID: PMC10722842 DOI: 10.1186/s40824-023-00465-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 11/20/2023] [Indexed: 12/17/2023] Open
Abstract
BACKGROUND Drug nanocarriers can markedly reduce the toxicities and side effects of encapsulated chemotherapeutic drugs in the clinic. However, these drug nanocarriers have little effect on eradicating breast cancer stem cells (BCSCs). Although compounds that can inhibit BCSCs have been reported, these compounds are difficult to use as carriers for the widespread delivery of conventional chemotherapeutic drugs. METHODS Herein, we synthesize a polymeric nanocarrier, hyaluronic acid-block-poly (curcumin-dithiodipropionic acid) (HA-b-PCDA), and explore the use of HA-b-PCDA to simultaneously deliver chemotherapeutic drugs and eradicate BCSCs. RESULTS Based on molecular docking and molecular dynamics studies, HA-b-PCDA delivers 35 clinical chemotherapeutic drugs. To further verify the drug deliver ability of HA-b-PCDA, doxorubicin, paclitaxel, docetaxel, gemcitabine and camptothecin are employed as model drugs to prepare nanoparticles. These drug-loaded HA-b-PCDA nanoparticles significantly inhibit the proliferation and stemness of BCSC-enriched 4T1 mammospheres. Moreover, doxorubicin-loaded HA-b-PCDA nanoparticles efficiently inhibit tumor growth and eradicate approximately 95% of BCSCs fraction in vivo. Finally, HA-b-PCDA eradicates BCSCs by activating Hippo and inhibiting the JAK2/STAT3 pathway. CONCLUSION HA-b-PCDA is a polymeric nanocarrier that eradicates BCSCs and potentially delivers numerous clinical chemotherapeutic drugs.
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Affiliation(s)
- Li Lv
- Department of Pharmacy, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510120, China
| | - Yonghui Shi
- Department of Pharmacy, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510120, China
| | - Zhicheng Deng
- Shenshan Medical Center, Memorial Hospital of Sun Yat-Sen University, Shanwei, Guangdong, 516600, China
| | - Jiajia Xu
- School of Pharmacy, Guangxi Medical University, Nanning, Guangxi, 530021, China
| | - Zicong Ye
- Department of Pharmacy, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510120, China
| | - Jianxiong He
- Department of Pharmacy, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510120, China
| | - Guanghui Chen
- Department of Pharmacy, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510120, China
| | - Xiaoxia Yu
- Department of Pharmacy, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510120, China
| | - Junyan Wu
- Department of Pharmacy, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510120, China.
| | - Xingzhen Huang
- School of Pharmacy, Guangxi Medical University, Nanning, Guangxi, 530021, China.
| | - Guocheng Li
- Department of Pharmacy, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510120, China.
- Shenshan Medical Center, Memorial Hospital of Sun Yat-Sen University, Shanwei, Guangdong, 516600, China.
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11
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Izadpanah A, Mohammadkhani N, Masoudnia M, Ghasemzad M, Saeedian A, Mehdizadeh H, Poorebrahim M, Ebrahimi M. Update on immune-based therapy strategies targeting cancer stem cells. Cancer Med 2023; 12:18960-18980. [PMID: 37698048 PMCID: PMC10557910 DOI: 10.1002/cam4.6520] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 08/16/2023] [Accepted: 08/30/2023] [Indexed: 09/13/2023] Open
Abstract
Accumulating data reveals that tumors possess a specialized subset of cancer cells named cancer stem cells (CSCs), responsible for metastasis and recurrence of malignancies, with various properties such as self-renewal, heterogenicity, and capacity for drug resistance. Some signaling pathways or processes like Notch, epithelial to mesenchymal transition (EMT), Hedgehog (Hh), and Wnt, as well as CSCs' surface markers such as CD44, CD123, CD133, and epithelial cell adhesion molecule (EpCAM) have pivotal roles in acquiring CSCs properties. Therefore, targeting CSC-related signaling pathways and surface markers might effectively eradicate tumors and pave the way for cancer survival. Since current treatments such as chemotherapy and radiation therapy cannot eradicate all of the CSCs and tumor relapse may happen following temporary recovery, improving novel and more efficient therapeutic options to combine with current treatments is required. Immunotherapy strategies are the new therapeutic modalities with promising results in targeting CSCs. Here, we review the targeting of CSCs by immunotherapy strategies such as dendritic cell (DC) vaccines, chimeric antigen receptors (CAR)-engineered immune cells, natural killer-cell (NK-cell) therapy, monoclonal antibodies (mAbs), checkpoint inhibitors, and the use of oncolytic viruses (OVs) in pre-clinical and clinical studies. This review will mainly focus on blood malignancies but also describe solid cancers.
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Affiliation(s)
- Amirhossein Izadpanah
- Department of Stem Cells and Developmental Biology, Cell Science Research CenterRoyan Institute for Stem Cell Biology and Technology, ACECRTehranIran
| | - Niloufar Mohammadkhani
- Department of Clinical BiochemistrySchool of Medicine, Shahid Beheshti University of Medical SciencesTehranIran
| | - Mina Masoudnia
- Department of ImmunologySchool of Medicine, Shahid Beheshti University of Medical SciencesTehranIran
| | - Mahsa Ghasemzad
- Department of Stem Cells and Developmental Biology, Cell Science Research CenterRoyan Institute for Stem Cell Biology and Technology, ACECRTehranIran
- Department of Molecular Cell Biology‐Genetics, Faculty of Basic Sciences and Advanced Technologies in BiologyUniversity of Science and CultureTehranIran
| | - Arefeh Saeedian
- Radiation Oncology Research CenterCancer Research Institute, Tehran University of Medical SciencesTehranIran
- Department of Radiation OncologyCancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical SciencesTehranIran
| | - Hamid Mehdizadeh
- Department of Stem Cells and Developmental Biology, Cell Science Research CenterRoyan Institute for Stem Cell Biology and Technology, ACECRTehranIran
| | - Mansour Poorebrahim
- Arnie Charbonneau Cancer Research Institute, University of CalgaryAlbertaCalgaryCanada
| | - Marzieh Ebrahimi
- Department of Stem Cells and Developmental Biology, Cell Science Research CenterRoyan Institute for Stem Cell Biology and Technology, ACECRTehranIran
- Department of regenerative medicineCell Science research Center, Royan Institute for stem cell biology and technology, ACECRTehranIran
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12
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Sravani A, Chandrasekaran N, Thomas J, Mukherjee A. Formulation and characterization of cisplatin-loaded hydroxyl functionalized single-walled carbon nanotubes for targeting gastric cancer stem cells. Heliyon 2023; 9:e18798. [PMID: 37593603 PMCID: PMC10432176 DOI: 10.1016/j.heliyon.2023.e18798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 07/27/2023] [Accepted: 07/27/2023] [Indexed: 08/19/2023] Open
Abstract
Chemotherapy is the most commonly used therapeutic method for treating many malignancies including gastric cancer. Due to their non-specific and non-targeted drug delivery, it causes resistance leading to cancer progression, relapse, and metastasis of cancer. To overcome this problem we carried out a study aimed to develop a new cisplatin (Cisp) loaded hydroxyl functionalized single-walled carbon nanotube (OH-SWCNT) nanocarrier system to selectively eliminate gastric cancer stem cells. To our understanding, this is the first study of the non-covalent interaction of cisplatin loaded on the surface of hydroxyl-functionalized single-walled carbon nanotubes by ultrasonication. The physical and morphological characterization was carried out by UV-Vis, FTIR spectroscopy, and TEM. A sustained and controlled release of cisp from OH-SWCNT at all three pHs 3.5, 5.5, and 7.4 was observed. Gastric cancer stem cells were isolated from primary cells and were identified by using CD133+ and CD44+ specific markers. Cisplatin-loaded OH-SWCNT nanocarrier was capable of limiting the self-renewal capacity of both CD133+ and CD44+ populations and also decreasing the number of tumorspheres in gastric CSCs. The cell viability percent of AGS cells was 20% at 250 μg/ml concentration. The IC50 value was less than 50% mol/L at both 200 μg/ml and 250 μg/ml of cisplatin-loaded OH-SWCNT. Our findings suggest that cisplatin-loaded OH-SWCNT nanocarrier complexes could target gastric CSCs and also could provide a potential strategy for selectively targeting and efficiently eliminating gastric CSCs. This could be a promising approach to prevent gastric cancer recurrence and metastasis and also improve gastric cancer therapy.
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Affiliation(s)
- A.N.K.V. Sravani
- Centre for Nanobiotechnology, Vellore Institute of Technology (VIT), Vellore, 632014, Tamil Nadu, India
| | - Natarajan Chandrasekaran
- Centre for Nanobiotechnology, Vellore Institute of Technology (VIT), Vellore, 632014, Tamil Nadu, India
| | - John Thomas
- Centre for Nanobiotechnology, Vellore Institute of Technology (VIT), Vellore, 632014, Tamil Nadu, India
| | - Amitava Mukherjee
- Centre for Nanobiotechnology, Vellore Institute of Technology (VIT), Vellore, 632014, Tamil Nadu, India
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13
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Yue M, Guo T, Nie DY, Zhu YX, Lin M. Advances of nanotechnology applied to cancer stem cells. World J Stem Cells 2023; 15:514-529. [PMID: 37424953 PMCID: PMC10324502 DOI: 10.4252/wjsc.v15.i6.514] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 03/01/2023] [Accepted: 04/18/2023] [Indexed: 06/26/2023] Open
Abstract
Cancer stem cells (CSCs) are a small proportion of the cells that exist in cancer tissues. They are considered to be the culprit of tumor genesis, development, drug resistance, metastasis and recurrence because of their self-renewal, proliferation, and differentiation potential. The elimination of CSCs is thus the key to cure cancer, and targeting CSCs provides a new method for tumor treatment. Due to the advantages of controlled sustained release, targeting and high biocompatibility, a variety of nanomaterials are used in the diagnosis and treatments targeting CSCs and promote the recognition and removal of tumor cells and CSCs. This article mainly reviews the research progress of nanotechnology in sorting CSCs and nanodrug delivery systems targeting CSCs. Furthermore, we identify the problems and future research directions of nanotechnology in CSC therapy. We hope that this review will provide guidance for the design of nanotechnology as a drug carrier so that it can be used in clinic for cancer therapy as soon as possible.
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Affiliation(s)
- Miao Yue
- Clinical Laboratory, Nanjing University of Chinese Medicine, Taizhou 225300, Jiangsu Province, China
| | - Ting Guo
- Taizhou School of Clinical Medicine, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou 225300, Jiangsu Province, China
| | - Deng-Yun Nie
- Clinical Laboratory, Nanjing University of Chinese Medicine, Taizhou 225300, Jiangsu Province, China
| | - Yin-Xing Zhu
- Taizhou School of Clinical Medicine, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou 225300, Jiangsu Province, China
| | - Mei Lin
- Taizhou School of Clinical Medicine, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou 225300, Jiangsu Province, China.
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14
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Sun L, Yao HJ, Li JC, Zhao BQ, Wang YA, Zhang YG. Activated Carbon nanoparticles Loaded with Metformin for Effective Against Hepatocellular Cancer Stem Cells. Int J Nanomedicine 2023; 18:2891-2910. [PMID: 37283712 PMCID: PMC10239765 DOI: 10.2147/ijn.s382519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 04/16/2023] [Indexed: 06/08/2023] Open
Abstract
Introduction Hepatocellular cancer stem cells (CSCs) play crucial roles in hepatocellular cancer initiation, development, relapse, and metastasis. Therefore, eradication of this cell population is a primary objective in hepatocellular cancer therapy. We prepared a nanodrug delivery system with activated carbon nanoparticles (ACNP) as carriers and metformin (MET) as drug (ACNP-MET), which was able to selectively eliminate hepatocellular CSCs and thereby increase the effects of MET on hepatocellular cancers. Methods ACNP were prepared by ball milling and deposition in distilled water. Suspension of ACNP and MET was mixed and the best ratio of ACNP and MET was determined based on the isothermal adsorption formula. Hepatocellular CSCs were identified as CD133+ cells and cultured in serum-free medium. We investigated the effects of ACNP-MET on hepatocellular CSCs, including the inhibitory effects, the targeting efficiency, self-renewal capacity, and the sphere-forming capacity of hepatocellular CSCs. Next, we evaluated the therapeutic efficacy of ACNP-MET by using in vivo relapsed tumor models of hepatocellular CSCs. Results The ACNP have a similar size, a regular spherical shape and a smooth surface. The optimal ratio for adsorption was MET: ACNP=1:4. ACNP-MET could target and inhibit the proliferation of CD133+ population and decrease mammosphere formation and renewal of CD133+ population in vitro and in vivo. Conclusion These results not only suggest that nanodrug delivery system increased the effects of MET, but also shed light on the mechanisms of the therapeutic effects of MET and ACNP-MET on hepatocellular cancers. ACNP, as a good nano-carrier, could strengthen the effect of MET by carrying drugs to the micro-environment of hepatocellular CSCs.
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Affiliation(s)
- Lan Sun
- Key Laboratory of Nanopharmacology and Nanotoxicology, Beijing Institute of Pharmacology and Toxicology, Beijing, People’s Republic of China
| | - Hong-Juan Yao
- Key Laboratory of Antibiotic Bioengineering of National Health and Family Planning Commission (NHFPC), Institute of Medicinal Biotechnology (IMB), Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, People’s Republic of China
| | - Jing-Cao Li
- Key Laboratory of Nanopharmacology and Nanotoxicology, Beijing Institute of Pharmacology and Toxicology, Beijing, People’s Republic of China
| | - Bao-Quan Zhao
- Key Laboratory of Nanopharmacology and Nanotoxicology, Beijing Institute of Pharmacology and Toxicology, Beijing, People’s Republic of China
| | - Yong-An Wang
- Key Laboratory of Nanopharmacology and Nanotoxicology, Beijing Institute of Pharmacology and Toxicology, Beijing, People’s Republic of China
| | - Ying-Ge Zhang
- Key Laboratory of Nanopharmacology and Nanotoxicology, Beijing Institute of Pharmacology and Toxicology, Beijing, People’s Republic of China
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15
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Haque M, Shakil MS, Mahmud KM. The Promise of Nanoparticles-Based Radiotherapy in Cancer Treatment. Cancers (Basel) 2023; 15:cancers15061892. [PMID: 36980778 PMCID: PMC10047050 DOI: 10.3390/cancers15061892] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 03/13/2023] [Accepted: 03/15/2023] [Indexed: 03/30/2023] Open
Abstract
Radiation has been utilized for a long time for the treatment of cancer patients. However, radiotherapy (RT) has many constraints, among which non-selectivity is the primary one. The implementation of nanoparticles (NPs) with RT not only localizes radiation in targeted tissue but also provides significant tumoricidal effect(s) compared to radiation alone. NPs can be functionalized with both biomolecules and therapeutic agents, and their combination significantly reduces the side effects of RT. NP-based RT destroys cancer cells through multiple mechanisms, including ROS generation, which in turn damages DNA and other cellular organelles, inhibiting of the DNA double-strand damage-repair system, obstructing of the cell cycle, regulating of the tumor microenvironment, and killing of cancer stem cells. Furthermore, such combined treatments overcome radioresistance and drug resistance to chemotherapy. Additionally, NP-based RT in combined treatments have shown synergistic therapeutic benefit(s) and enhanced the therapeutic window. Furthermore, a combination of phototherapy, i.e., photodynamic therapy and photothermal therapy with NP-based RT, not only reduces phototoxicity but also offers excellent therapeutic benefits. Moreover, using NPs with RT has shown promise in cancer treatment and shown excellent therapeutic outcomes in clinical trials. Therefore, extensive research in this field will pave the way toward improved RT in cancer treatment.
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Affiliation(s)
- Munima Haque
- Department of Mathematics and Natural Sciences, BRAC University, Dhaka 1212, Bangladesh
| | - Md Salman Shakil
- Department of Mathematics and Natural Sciences, BRAC University, Dhaka 1212, Bangladesh
| | - Kazi Mustafa Mahmud
- Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh
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16
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Zhao Y, Zheng Y, Zhu Y, Ding K, Zhou M, Liu T. Co-delivery of gemcitabine and Triapine by calcium carbonate nanoparticles against chemoresistant pancreatic cancer. Int J Pharm 2023; 636:122844. [PMID: 36925025 DOI: 10.1016/j.ijpharm.2023.122844] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Revised: 02/14/2023] [Accepted: 03/11/2023] [Indexed: 03/16/2023]
Abstract
Pancreatic cancer is a malignant disease with high mortality, and its systemic treatment strategy mainly focuses on chemotherapy. Yet, the overall prognosis of pancreatic cancer patients is still extremely poor with a low survival rate. Gemcitabine (GEM) is a widely used chemotherapeutic agent for the treatment of pancreatic cancer. However, GEM chemoresistance remains the major challenge. In this study, we prepared calcium carbonate nanoparticles (CaCO3 NPs) loaded with a nucleotide reductase inhibitor (Triapine) and GEM to suppress the GEM resistance of pancreatic cancer cells (PANC-1/GEM) and solve the problem of poor solubility of Triapine. CaCO3-GEM-Triapine NPs nano-formulations enhanced the therapeutic effect of GEM-based chemotherapy by inhibiting cancer cell proliferation, migration, and resistance to GEM using both 2D PANC-1/GEM cells and 3D tumor spheroids. The study indicated that CaCO3 NPs loaded with GEM and Triapine could provide an effective treatment option to overcome drug resistance in pancreatic cancer.
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Affiliation(s)
- Yongmei Zhao
- School of Pharmacy, Nantong University, Nantong, China
| | - Yuanlin Zheng
- School of Pharmacy, Nantong University, Nantong, China
| | - Yan Zhu
- School of Pharmacy, Nantong University, Nantong, China
| | - Kai Ding
- School of Pharmacy, Nantong University, Nantong, China
| | - Mengjiao Zhou
- School of Pharmacy, Nantong University, Nantong, China.
| | - Tianqing Liu
- NICM Health Research Institute, Western Sydney University, Westmead, Australia.
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17
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Chauhan A, Alam MA, Kaur A, Malviya R. Advancements and Utilizations of Scaffolds in Tissue Engineering and Drug Delivery. Curr Drug Targets 2023; 24:13-40. [PMID: 36221880 DOI: 10.2174/1389450123666221011100235] [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: 01/05/2022] [Revised: 03/02/2022] [Accepted: 03/09/2022] [Indexed: 11/22/2022]
Abstract
The drug development process requires a thorough understanding of the scaffold and its three-dimensional structure. Scaffolding is a technique for tissue engineering and the formation of contemporary functioning tissues. Tissue engineering is sometimes referred to as regenerative medicine. They also ensure that drugs are delivered with precision. Information regarding scaffolding techniques, scaffolding kinds, and other relevant facts, such as 3D nanostructuring, are discussed in depth in this literature. They are specific and demonstrate localized action for a specific reason. Scaffold's acquisition nature and flexibility make it a new drug delivery technology with good availability and structural parameter management.
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Affiliation(s)
- Akash Chauhan
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
| | - Md Aftab Alam
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
| | - Awaneet Kaur
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
| | - Rishabha Malviya
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
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18
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Nayak A, Warrier NM, Kumar P. Cancer Stem Cells and the Tumor Microenvironment: Targeting the Critical Crosstalk through Nanocarrier Systems. Stem Cell Rev Rep 2022; 18:2209-2233. [PMID: 35876959 PMCID: PMC9489588 DOI: 10.1007/s12015-022-10426-9] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/10/2022] [Indexed: 11/25/2022]
Abstract
The physiological state of the tumor microenvironment (TME) plays a central role in cancer development due to multiple universal features that transcend heterogeneity and niche specifications, like promoting cancer progression and metastasis. As a result of their preponderant involvement in tumor growth and maintenance through several microsystemic alterations, including hypoxia, oxidative stress, and acidosis, TMEs make for ideal targets in both diagnostic and therapeutic ventures. Correspondingly, methodologies to target TMEs have been investigated this past decade as stratagems of significant potential in the genre of focused cancer treatment. Within targeted oncotherapy, nanomedical derivates-nanocarriers (NCs) especially-have emerged to present notable prospects in enhancing targeting specificity. Yet, one major issue in the application of NCs in microenvironmental directed therapy is that TMEs are too broad a spectrum of targeting possibilities for these carriers to be effectively employed. However, cancer stem cells (CSCs) might portend a solution to the above conundrum: aside from being quite heavily invested in tumorigenesis and therapeutic resistance, CSCs also show self-renewal and fluid clonogenic properties that often define specific TME niches. Further scrutiny of the relationship between CSCs and TMEs also points towards mechanisms that underly tumoral characteristics of metastasis, malignancy, and even resistance. This review summarizes recent advances in NC-enabled targeting of CSCs for more holistic strikes against TMEs and discusses both the current challenges that hinder the clinical application of these strategies as well as the avenues that can further CSC-targeting initiatives. Central role of CSCs in regulation of cellular components within the TME.
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Affiliation(s)
- Aadya Nayak
- Department of Biotechnology, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India
| | - Neerada Meenakshi Warrier
- Department of Biotechnology, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India
| | - Praveen Kumar
- Department of Biotechnology, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.
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19
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Rao X, Zhang C, Luo H, Zhang J, Zhuang Z, Liang Z, Wu X. Targeting Gastric Cancer Stem Cells to Enhance Treatment Response. Cells 2022; 11:cells11182828. [PMID: 36139403 PMCID: PMC9496718 DOI: 10.3390/cells11182828] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 09/02/2022] [Accepted: 09/05/2022] [Indexed: 11/16/2022] Open
Abstract
Gastric cancer (GC) was the fourth deadliest cancer in the world in 2020, and about 770,000 people died from GC that year. The death of patients with GC is mainly caused by the metastasis, recurrence, and chemotherapy resistance of GC cells. The cancer stem cell theory defines cancer stem cells (CSCs) as a key factor in the metastasis, recurrence, and chemotherapy resistance of cancer. It considers targeting gastric cancer stem cells (GCSCs) to be an effective method for the treatment of GC. For GCSCs, genes or noncoding RNAs are important regulatory factors. Many experimental studies have found that some drugs can target the stemness of gastric cancer by regulating these genes or noncoding RNAs, which may bring new directions for the clinical treatment of gastric cancer. Therefore, this review mainly discusses related genes or noncoding RNAs in GCSCs and drugs that target its stemness, thereby providing some information for the treatment of GC.
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20
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Chen Z, Zhuang J, Pang J, Liu Z, Zhang P, Deng H, Zhang L, Zhuang B. Application of a cationic amylose derivative loaded with single-walled carbon nanotubes for gene delivery therapy and photothermal therapy of colorectal cancer. J Biomed Mater Res A 2022; 110:1052-1061. [PMID: 34994069 PMCID: PMC9302136 DOI: 10.1002/jbm.a.37351] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 12/03/2021] [Accepted: 12/21/2021] [Indexed: 12/29/2022]
Abstract
Single-walled carbon nanotubes (SWNTs) are cylindrical graphitic helix molecules that exhibit superb mechanical and physical properties. Many polymers, such as polyethylene glycol and glycated chitosan, have been used to modify SWNTs to enhance the stability and biocompatibility of delivery systems; thus, a novel modification for SWNTs with amylose derivatives containing poly(L-lysine) dendrons (ADP@SWNT) is developed. Infrared spectra analysis, 1 H NMR analysis, circular dichroism spectra analysis and thermogravimetric analysis are used to characterize and confirm complex formation. The aqueous dispersion stability, cytotoxicity, gene transfection efficiency and photothermal effect of the complex are studied in vitro and in vivo. Results suggest that the ADP@SWNT complex is successfully synthesized with good water dispersion stability and pDNA transfection capacity. ADP@SWNT/TNFα inhibits tumor growth and metastasis both in vivo and in vitro, and the anti-tumor effect is enhanced by NIR irradiation, suggesting its high potential for application in tumor therapy.
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Affiliation(s)
- Zechang Chen
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal TumorNanfang Hospital, Southern Medical UniversityGuangzhouChina
| | - Junbo Zhuang
- The First School of Clinical MedicineSouthern Medical UniversityGuangzhouChina
| | - Jiadong Pang
- Institute of Polymer Science, Department of Polymer and Materials Science, School of Chemistry and Chemical EngineeringSun Yat‐Sen UniversityGuangzhouChina
| | - Zehao Liu
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal TumorNanfang Hospital, Southern Medical UniversityGuangzhouChina
| | - Penghao Zhang
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal TumorNanfang Hospital, Southern Medical UniversityGuangzhouChina
| | - Haijun Deng
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal TumorNanfang Hospital, Southern Medical UniversityGuangzhouChina
| | - Liming Zhang
- Institute of Polymer Science, Department of Polymer and Materials Science, School of Chemistry and Chemical EngineeringSun Yat‐Sen UniversityGuangzhouChina
| | - Baoxiong Zhuang
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal TumorNanfang Hospital, Southern Medical UniversityGuangzhouChina
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21
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Yang Y, Meng WJ, Wang ZQ. Cancer Stem Cells and the Tumor Microenvironment in Gastric Cancer. Front Oncol 2022; 11:803974. [PMID: 35047411 PMCID: PMC8761735 DOI: 10.3389/fonc.2021.803974] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Accepted: 12/08/2021] [Indexed: 02/05/2023] Open
Abstract
Gastric cancer (GC) remains one of the leading causes of cancer-related death worldwide. Cancer stem cells (CSCs) might be responsible for tumor initiation, relapse, metastasis and treatment resistance of GC. The tumor microenvironment (TME) comprises tumor cells, immune cells, stromal cells and other extracellular components, which plays a pivotal role in tumor progression and therapy resistance. The properties of CSCs are regulated by cells and extracellular matrix components of the TME in some unique manners. This review will summarize current literature regarding the effects of CSCs and TME on the progression and therapy resistance of GC, while emphasizing the potential for developing successful anti-tumor therapy based on targeting the TME and CSCs.
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Affiliation(s)
| | - Wen-Jian Meng
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
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22
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Kearns O, Camisasca A, Giordani S. Hyaluronic Acid-Conjugated Carbon Nanomaterials for Enhanced Tumour Targeting Ability. Molecules 2021; 27:48. [PMID: 35011272 PMCID: PMC8746509 DOI: 10.3390/molecules27010048] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 12/13/2021] [Accepted: 12/20/2021] [Indexed: 12/31/2022] Open
Abstract
Hyaluronic acid (HA) has been implemented for chemo and photothermal therapy to target tumour cells overexpressing the CD44+ receptor. HA-targeting hybrid systems allows carbon nanomaterial (CNM) carriers to efficiently deliver anticancer drugs, such as doxorubicin and gemcitabine, to the tumour sites. Carbon nanotubes (CNTs), graphene, graphene oxide (GO), and graphene quantum dots (GQDs) are grouped for a detailed review of the novel nanocomposites for cancer therapy. Some CNMs proved to be more successful than others in terms of stability and effectiveness at removing relative tumour volume. While the literature has been focused primarily on the CNTs and GO, other CNMs such as carbon nano-onions (CNOs) proved quite promising for targeted drug delivery using HA. Near-infrared laser photoablation is also reviewed as a primary method of cancer therapy-it can be used alone or in conjunction with chemotherapy to achieve promising chemo-photothermal therapy protocols. This review aims to give a background into HA and why it is a successful cancer-targeting component of current CNM-based drug delivery systems.
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Affiliation(s)
| | | | - Silvia Giordani
- School of Chemical Sciences, Dublin City University, Glasnevin, D09 E432 Dublin, Ireland; (O.K.); (A.C.)
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23
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Qi D, Liu Y, Li J, Huang JH, Hu X, Wu E. Salinomycin as a potent anticancer stem cell agent: State of the art and future directions. Med Res Rev 2021; 42:1037-1063. [PMID: 34786735 PMCID: PMC9298915 DOI: 10.1002/med.21870] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 10/22/2021] [Accepted: 10/26/2021] [Indexed: 12/11/2022]
Abstract
Cancer stem cells (CSCs) are a small subpopulation of cells within a tumor that can both self‐renew and differentiate into other cell types forming the heterogeneous tumor bulk. Since CSCs are involved in all aspects of cancer development, including tumor initiation, cell proliferation, metastatic dissemination, therapy resistance, and recurrence, they have emerged as attractive targets for cancer treatment and management. Salinomycin, a widely used antibiotic in poultry farming, was identified by the Weinberg group as a potent anti‐CSC agent in 2009. As a polyether ionophore, salinomycin exerts broad‐spectrum activities, including the important anti‐CSC function. Studies on the mechanism of action of salinomycin against cancer have been continuously and rapidly published since then. Thus, it is imperative for us to update its literature of recent research findings in this area. We here summarize the notable work reported on salinomycin's anticancer activities, intracellular binding target(s), effects on tumor microenvironment, safety, derivatives, and tumor‐specific drug delivery; after that we also discuss the translational potential of salinomycin toward clinical application based on current multifaceted understandings.
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Affiliation(s)
- Dan Qi
- Department of Neurosurgery, Baylor Scott & White Health, Temple, Texas, USA.,Neuroscience Institute, Baylor Scott & White Health, Temple, Texas, USA
| | - Yunyi Liu
- Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Collaborative Innovation Center for Molecular Engineering for Theranostics, Hunan University, Changsha, China
| | - Juan Li
- Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Collaborative Innovation Center for Molecular Engineering for Theranostics, Hunan University, Changsha, China
| | - Jason H Huang
- Department of Neurosurgery, Baylor Scott & White Health, Temple, Texas, USA.,Neuroscience Institute, Baylor Scott & White Health, Temple, Texas, USA.,Department of Surgery, Texas A&M University College of Medicine, Temple, Texas, USA
| | - Xiaoxiao Hu
- Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Collaborative Innovation Center for Molecular Engineering for Theranostics, Hunan University, Changsha, China.,Shenzhen Research Institute, Hunan University, Shenzhen, Guangdong, China
| | - Erxi Wu
- Department of Neurosurgery, Baylor Scott & White Health, Temple, Texas, USA.,Neuroscience Institute, Baylor Scott & White Health, Temple, Texas, USA.,Department of Surgery, Texas A&M University College of Medicine, Temple, Texas, USA.,LIVESTRONG Cancer Institutes and Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, Texas, USA.,Department of Pharmaceutical Sciences, Texas A&M University College of Pharmacy, College Station, Texas, USA
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24
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Zhao Y, Zheng Y, Zhu Y, Zhang Y, Zhu H, Liu T. M1 Macrophage-Derived Exosomes Loaded with Gemcitabine and Deferasirox against Chemoresistant Pancreatic Cancer. Pharmaceutics 2021; 13:pharmaceutics13091493. [PMID: 34575569 PMCID: PMC8472397 DOI: 10.3390/pharmaceutics13091493] [Citation(s) in RCA: 66] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 09/11/2021] [Accepted: 09/14/2021] [Indexed: 11/16/2022] Open
Abstract
Pancreatic cancer is a malignant disease with high mortality and poor prognosis due to lack of early diagnosis and low treatment efficiency after diagnosis. Although Gemcitabine (GEM) is used as the first-line chemotherapeutic drug, chemoresistance is still the major problem that limits its therapeutic efficacy. Here in this study, we developed a specific M1 macrophage-derived exosome (M1Exo)-based drug delivery system against GEM resistance in pancreatic cancer. In addition to GEM, Deferasirox (DFX) was also loaded into drug carrier, M1Exo, in order to inhibit ribonucleotide reductase regulatory subunit M2 (RRM2) expression via depleting iron, and thus increase chemosensitivity of GEM. The M1Exo nanoformulations combining both GEM and DFX significantly enhanced the therapeutic efficacy on the GEM-resistant PANC-1/GEM cells and 3D tumor spheroids by inhibiting cancer cell proliferation, cell attachment and migration, and chemoresistance to GEM. These data demonstrated that M1Exo loaded with GEM and DFX offered an efficient therapeutic strategy for drug-resistant pancreatic cancer.
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Affiliation(s)
- Yongmei Zhao
- School of Pharmacy, Nantong University, Nantong 226019, China; (Y.Z.); (Y.Z.); (Y.Z.); (H.Z.)
| | - Yuanlin Zheng
- School of Pharmacy, Nantong University, Nantong 226019, China; (Y.Z.); (Y.Z.); (Y.Z.); (H.Z.)
| | - Yan Zhu
- School of Pharmacy, Nantong University, Nantong 226019, China; (Y.Z.); (Y.Z.); (Y.Z.); (H.Z.)
| | - Yi Zhang
- School of Chemistry, University of Glasgow, Glasgow G12 8QQ, UK;
| | - Hongyan Zhu
- School of Pharmacy, Nantong University, Nantong 226019, China; (Y.Z.); (Y.Z.); (Y.Z.); (H.Z.)
| | - Tianqing Liu
- NICM Health Research Institute, Western Sydney University, Sydney, NSW 2145, Australia
- Correspondence:
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25
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Zhang M, Gao S, Yang D, Fang Y, Lin X, Jin X, Liu Y, Liu X, Su K, Shi K. Influencing factors and strategies of enhancing nanoparticles into tumors in vivo. Acta Pharm Sin B 2021; 11:2265-2285. [PMID: 34522587 PMCID: PMC8424218 DOI: 10.1016/j.apsb.2021.03.033] [Citation(s) in RCA: 111] [Impact Index Per Article: 27.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Revised: 01/05/2021] [Accepted: 02/03/2021] [Indexed: 02/07/2023] Open
Abstract
The administration of nanoparticles (NPs) first faces the challenges of evading renal filtration and clearance of reticuloendothelial system (RES). After that, NPs infiltrate through the expanded endothelial space and penetrated the dense stroma of tumor microenvironment to tumor cells. As long as possible to prolong the time of NPs remaining in tumor tissue, NPs release active agent and induce pharmacological action. This review provides a comprehensive summary of the physical and chemical properties of NPs and the influence of various biological factors in tumor microenvironment, and discusses how to improve the final efficacy through adjusting the characteristics and structure of NPs. Perspectives and future directions are also provided.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Kai Shi
- Corresponding author. Tel./fax: +86 24 43520557.
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26
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Tefas LR, Barbălată C, Tefas C, Tomuță I. Salinomycin-Based Drug Delivery Systems: Overcoming the Hurdles in Cancer Therapy. Pharmaceutics 2021; 13:pharmaceutics13081120. [PMID: 34452081 PMCID: PMC8401311 DOI: 10.3390/pharmaceutics13081120] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/28/2021] [Accepted: 07/19/2021] [Indexed: 12/11/2022] Open
Abstract
Cancer stem cells (CSCs) are reportedly responsible for the initiation and propagation of cancer. Since CSCs are highly resistant to conventional chemo- and radiotherapy, they are considered the main cause of cancer relapse and metastasis. Salinomycin (Sali), an anticoccidial polyether antibiotic, has emerged as a promising new candidate for cancer therapy, with selective cytotoxicity against CSCs in various malignancies. Nanotechnology provides an efficient means of delivering Sali to tumors in view of reducing collateral damage to healthy tissues and enhancing the therapeutic outcome. This review offers an insight into the most recent advances in cancer therapy using Sali-based nanocarriers.
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Affiliation(s)
- Lucia Ruxandra Tefas
- Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania; (L.R.T.); (C.B.); (I.T.)
| | - Cristina Barbălată
- Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania; (L.R.T.); (C.B.); (I.T.)
| | - Cristian Tefas
- Department of Gastroenterology, “Prof. Dr. Octavian Fodor” Regional Institute for Gastroenterology and Hepatology, 19–21 Croitorilor Street, 400162 Cluj-Napoca, Romania
- Department of Internal Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 8 Victor Babeș Street, 400012 Cluj-Napoca, Romania
- Correspondence: ; Tel.: +40-740836136
| | - Ioan Tomuță
- Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania; (L.R.T.); (C.B.); (I.T.)
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27
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Sinolits AV, Chernysheva MG, Popov AG, Egorov AV, Badun GA. Hyaluronic acid adsorption on nanodiamonds: Quantitative characteristics and mechanism. Colloids Surf A Physicochem Eng Asp 2021. [DOI: 10.1016/j.colsurfa.2021.126461] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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28
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Molecular targeted treatment and drug delivery system for gastric cancer. J Cancer Res Clin Oncol 2021; 147:973-986. [PMID: 33550445 DOI: 10.1007/s00432-021-03520-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 01/10/2021] [Indexed: 12/24/2022]
Abstract
Gastric cancer is still a major cancer worldwide. The early diagnosis rate of gastric cancer in most high incidence countries is low. At present, the overall treatment effect of gastric cancer is poor, and the median overall survival remains low. Most of the patients with gastric cancer are in an advanced stage when diagnosed, and drug treatment has become the main means. Thus, new targeted drugs and therapeutic strategies are the hope of improving the therapeutic effect of gastric cancer. In this review, we summarize the new methods and advances of targeted therapy for gastric cancer, including novel molecular targeted therapeutic agents and drug delivery systems, with a major focus on the development of drug delivery systems (drug carriers and targeting peptides). Elaborating these new methods and advances will contribute to the management of gastric cancer.
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29
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Dugam S, Nangare S, Patil P, Jadhav N. Carbon dots: A novel trend in pharmaceutical applications. ANNALES PHARMACEUTIQUES FRANÇAISES 2021; 79:335-345. [PMID: 33383021 DOI: 10.1016/j.pharma.2020.12.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 12/09/2020] [Accepted: 12/17/2020] [Indexed: 12/15/2022]
Abstract
Carbon quantum dots (CQDs, C-dots, or CDs), are generally small carbon nanoparticles having a size less than 10nm. Carbon dots (CDs) were accidentally discovered during the purification of single-walled carbon nanotubes through preparative electrophoresis in 2004. Carbon is an organic material having poor water solubility that emits less fluorescence. However, CDs have good aqueous solubility and excellent fluorescent property, hence more attention has been given to the synthesis of CDs and their applications in chemistry and allied sciences. CDs being easily accessible for in-house synthesis, simpler fabrication as per compendial requirements are wisely accepted. In addition, since CDs are biocompatible, of low toxicity, and of biodegradable nature, they appear as a promising tool for the health care sector. Furthermore, owing to their capabilities of expressing significant interaction with biological materials, and their excellent photoluminescence (PL), CDs have been emerging as novel pioneered nanoparticles useful for pharmaceutical and theranostic applications. Also, CDs are more eco-friendly in synthesis and therefore can be favorably consumed as alternatives in the further development of biological, environmental, and food areas. A massive study has been performed dealing with different approaches which are adopted for CDs synthesis and their applications as, filters for the separation of pollutants from polluted water, food safety, toxicological studies, and optical properties, etc. While still less emphasis is given on the applications of CDs in pharmaceuticals like for sustained and targeted drug delivery systems, theranostic study, etc. Hence, in the present review, we are exploring CQDs as a boon to pharmaceutical concerns.
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Affiliation(s)
- S Dugam
- Department of Pharmaceutics, Bharati-Vidyapeeth College of Pharmacy, 416013 Kolhapur, Maharashtra state, India
| | - S Nangare
- Department of Pharmaceutical Chemistry, H. R. Patel Institute of Pharmaceutical Education and Research, 425405 Shirpur, Maharashtra state, India
| | - P Patil
- Department of Pharmaceutical Chemistry, H. R. Patel Institute of Pharmaceutical Education and Research, 425405 Shirpur, Maharashtra state, India
| | - N Jadhav
- Department of Pharmaceutics, Bharati-Vidyapeeth College of Pharmacy, 416013 Kolhapur, Maharashtra state, India.
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30
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Duan H, Liu Y, Gao Z, Huang W. Recent advances in drug delivery systems for targeting cancer stem cells. Acta Pharm Sin B 2021; 11:55-70. [PMID: 33532180 PMCID: PMC7838023 DOI: 10.1016/j.apsb.2020.09.016] [Citation(s) in RCA: 153] [Impact Index Per Article: 38.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 06/25/2020] [Accepted: 07/12/2020] [Indexed: 02/07/2023] Open
Abstract
Cancer stem cells (CSCs) are a subpopulation of cancer cells with functions similar to those of normal stem cells. Although few in number, they are capable of self-renewal, unlimited proliferation, and multi-directional differentiation potential. In addition, CSCs have the ability to escape immune surveillance. Thus, they play an important role in the occurrence and development of tumors, and they are closely related to tumor invasion, metastasis, drug resistance, and recurrence after treatment. Therefore, specific targeting of CSCs may improve the efficiency of cancer therapy. A series of corresponding promising therapeutic strategies based on CSC targeting, such as the targeting of CSC niche, CSC signaling pathways, and CSC mitochondria, are currently under development. Given the rapid progression in this field and nanotechnology, drug delivery systems (DDSs) for CSC targeting are increasingly being developed. In this review, we summarize the advances in CSC-targeted DDSs. Furthermore, we highlight the latest developmental trends through the main line of CSC occurrence and development process; some considerations about the rationale, advantages, and limitations of different DDSs for CSC-targeted therapies were discussed.
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Key Words
- ABC, ATP binding cassette
- AFN, apoferritin
- ALDH, aldehyde dehydrogenase
- BM-MSCs-derived Exos, bone marrow mesenchymal stem cells-derived exosomes
- Biomarker
- CAFs, cancer-associated fibroblasts
- CL-siSOX2, cationic lipoplex of SOX2 small interfering RNA
- CMP, carbonate-mannose modified PEI
- CQ, chloroquine
- CSCs, cancer stem cells
- Cancer stem cells
- Cancer treatment
- Cellular level
- DCLK1, doublecortin-like kinase 1
- DDSs, drug delivery systems
- DLE, drug loading efficiency
- DOX, doxorubicin
- DQA-PEG2000-DSPE, dequlinium and carboxyl polyethylene glycol-distearoylphosphatidylethanolamine
- Dex, dexamethasone
- Drug delivery systems
- ECM, extracellular matrix
- EMT, epithelial–mesenchymal transition
- EPND, nanodiamond-Epirubicin drug complex
- EpCAM, epithelial cell adhesion molecule
- GEMP, gemcitabine monophosphate
- GLUT1, glucose ligand to the glucose transporter 1
- Glu, glucose
- HCC, hepatocellular carcinoma
- HH, Hedgehog
- HIF1α, hypoxia-inducible factor 1-alpha
- HNSCC, head and neck squamous cell carcinoma
- IONP, iron oxide nanoparticle
- LAC, lung adenocarcinoma
- LNCs, lipid nanocapsules
- MAPK, mitogen-activated protein kinase
- MB, methylene blue
- MDR, multidrug resistance
- MNP, micellar nanoparticle
- MSNs, mesoporous silica nanoparticles
- Molecular level
- NF-κB, nuclear factor-kappa B
- Nav, navitoclax
- Niche
- PBAEs, poly(β-aminoester)
- PDT, photodynamic therapy
- PEG-PCD, poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylene carbonate-graft-dodecanol)
- PEG-PLA, poly(ethylene glycol)-b-poly(d,l-lactide)
- PEG-b-PLA, poly(ethylene glycol)-block-poly(d,l-lactide)
- PLGA, poly(ethylene glycol)-poly(d,l-lactide-co-glycolide)
- PTX, paclitaxel
- PU-PEI, polyurethane-short branch-polyethylenimine
- SLNs, solid lipid nanoparticles
- SSCs, somatic stem cells
- Sali-ABA, 4-(aminomethyl) benzaldehyde-modified Sali
- TNBC, triple negative breast cancer
- TPZ, tirapazamine
- Targeting strategies
- cRGD, cyclic Arg-Gly-Asp
- iTEP, immune-tolerant, elastin-like polypeptide
- mAbs, monoclonal antibodies
- mPEG-b-PCC-g-GEM-g-DC-g-CAT, poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylenecarbonate-graft-dodecanol-graft-cationic ligands)
- ncRNA, non-coding RNAs
- uPAR, urokinase plasminogen activator receptor
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Affiliation(s)
- Hongxia Duan
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
| | - Yanhong Liu
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
| | - Zhonggao Gao
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
| | - Wei Huang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
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Chondroitin sulphate and α-tocopheryl succinate tethered multiwalled carbon nanotubes for dual-action therapy of triple-negative breast cancer. J Drug Deliv Sci Technol 2020. [DOI: 10.1016/j.jddst.2020.102080] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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32
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Oswald JT, Patel H, Khan D, Jeorje NN, Golzar H, Oswald EL, Tang S. Drug Delivery Systems Using Surface Markers for Targeting Cancer Stem Cells. Curr Pharm Des 2020; 26:2057-2071. [PMID: 32250211 DOI: 10.2174/1381612826666200406084900] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Accepted: 02/26/2020] [Indexed: 12/12/2022]
Abstract
The innate abilities of cancer stem cells (CSCs), such as multi-drug resistance, drug efflux, quiescence and ionizing radiation tolerance, protect them from most traditional chemotherapeutics. As a result, this small subpopulation of persistent cells leads to more aggressive and chemoresistant cancers, causing tumour relapse and metastasis. This subpopulation is differentiated from the bulk tumour population through a wide variety of surface markers expressed on the cell surface. Recent developments in nanomedicine and targeting delivery methods have given rise to new possibilities for specifically targeting these markers and preferentially eliminating CSCs. Herein, we first summarize the range of surface markers identifying CSC populations in a variety of cancers; then, we discuss recent attempts to actively target CSCs and their niches using liposomal, nanoparticle, carbon nanotube and viral formulations.
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Affiliation(s)
- James T Oswald
- School Of Nanotechnology Engineering, University of Waterloo, Waterloo, ON N2L 3G1, Canada
| | - Haritosh Patel
- School Of Nanotechnology Engineering, University of Waterloo, Waterloo, ON N2L 3G1, Canada
| | - Daid Khan
- School Of Nanotechnology Engineering, University of Waterloo, Waterloo, ON N2L 3G1, Canada
| | - Ninweh N Jeorje
- School Of Nanotechnology Engineering, University of Waterloo, Waterloo, ON N2L 3G1, Canada
| | - Hossein Golzar
- Department of Chemistry & Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, ON N2L 3G1, Canada
| | - Erin L Oswald
- School Of Nanotechnology Engineering, University of Waterloo, Waterloo, ON N2L 3G1, Canada
| | - Shirley Tang
- Department of Chemistry & Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, ON N2L 3G1, Canada
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Yao H, Sun L, Li J, Zhou X, Li R, Shao R, Zhang Y, Li L. A Novel Therapeutic siRNA Nanoparticle Designed for Dual-Targeting CD44 and Gli1 of Gastric Cancer Stem Cells. Int J Nanomedicine 2020; 15:7013-7034. [PMID: 33061365 PMCID: PMC7522319 DOI: 10.2147/ijn.s260163] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 08/07/2020] [Indexed: 12/24/2022] Open
Abstract
PURPOSE Gastric cancer stem cells (CSCs) are important for the initiation, growth, recurrence, and metastasis of gastric cancer, due to their chemo-resistance and indefinite proliferation. Herein, to eliminate gastric CSCs, we developed novel CSC-targeting glioma-associated oncogene homolog 1 (Gli1) small interfering RNA (siRNA) nanoparticles that are specifically guided by a di-stearoyl-phosphatidyl-ethanolamine- hyaluronic-acid (DSPE-HA) single-point conjugate, as an intrinsic ligand of the CD44 receptor. We refer to these as targeting Gli1 siRNA nanoparticles. METHODS We used the reductive amination reaction method for attaching amine groups of DSPE to aldehydic group of hyaluronic acid (HA) at the reducing end, to synthesize the DSPE-HA single-point conjugate. Next, targeting Gli1 siRNA nanoparticles were prepared using the layer-by-layer assembly method. We characterized the stem cellular features of targeting Gli1 siRNA nanoparticles, including their targeting efficiency, self-renewal capacity, the migration and invasion capacity of gastric CSCs, and the penetration ability of 3D tumor spheroids. Next, we evaluated the therapeutic efficacy of the targeting Gli1 siRNA nanoparticles by using in vivo relapsed tumor models of gastric CSCs. RESULTS Compared with the multipoint conjugates, DSPE-HA single-point conjugates on the surface of nanoparticles showed significantly higher binding affinities with CD44. The targeting Gli1 siRNA nanoparticles significantly decreased Gli1 protein expression, inhibited CSC tumor spheroid and colony formation, and suppressed cell migration and invasion. Furthermore, in vivo imaging demonstrated that targeting Gli1 siRNA nanoparticles accumulated in tumor tissues, showing significant antitumor recurrence efficacy in vivo. CONCLUSION In summary, our targeting Gli1 siRNA nanoparticles significantly inhibited CSC malignancy features by specifically blocking Hedgehog (Hh) signaling both in vitro and in vivo, suggesting that this novel siRNA delivery system that specifically eliminates gastric CSCs provides a promising targeted therapeutic strategy for gastric cancer treatment.
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Affiliation(s)
- Hongjuan Yao
- Key Laboratory of Antibiotic Bioengineering of National Health and Family Planning Commission (NHFPC), Institute of Medicinal Biotechnology (IMB), Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing100050, People’s Republic of China
| | - Lan Sun
- Key Laboratory of Nanopharmacology and Nanotoxicology, Beijing Institute of Pharmacology and Toxicology, Beijing100850, People’s Republic of China
| | - Jingcao Li
- Key Laboratory of Nanopharmacology and Nanotoxicology, Beijing Institute of Pharmacology and Toxicology, Beijing100850, People’s Republic of China
| | - Xiaofei Zhou
- Key Laboratory of Antibiotic Bioengineering of National Health and Family Planning Commission (NHFPC), Institute of Medicinal Biotechnology (IMB), Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing100050, People’s Republic of China
| | - Rui Li
- Key Laboratory of Antibiotic Bioengineering of National Health and Family Planning Commission (NHFPC), Institute of Medicinal Biotechnology (IMB), Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing100050, People’s Republic of China
| | - Rongguang Shao
- Key Laboratory of Antibiotic Bioengineering of National Health and Family Planning Commission (NHFPC), Institute of Medicinal Biotechnology (IMB), Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing100050, People’s Republic of China
| | - Yingge Zhang
- Key Laboratory of Nanopharmacology and Nanotoxicology, Beijing Institute of Pharmacology and Toxicology, Beijing100850, People’s Republic of China
| | - Liang Li
- Key Laboratory of Antibiotic Bioengineering of National Health and Family Planning Commission (NHFPC), Institute of Medicinal Biotechnology (IMB), Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing100050, People’s Republic of China
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34
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Role of Nrf2 and mitochondria in cancer stem cells; in carcinogenesis, tumor progression, and chemoresistance. Biochimie 2020; 179:32-45. [PMID: 32946993 DOI: 10.1016/j.biochi.2020.09.014] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Revised: 08/05/2020] [Accepted: 09/04/2020] [Indexed: 02/06/2023]
Abstract
Cancer stem cells (CSCs) are rare sub-population in tumor mass with self-renewal and differentiation abilities; CSCs are considered as the main cells which are responsible for tumor metastasis, cancer recurrence, and chemo/radio-resistance. CSCs are believed to contain low mitochondria in quantity, high concentration of nuclear factor erythroid 2-related factor 2 (Nrf2), and low reactive oxygen species (ROS) levels. Mitochondria regulate certain cellular functions, including controlling of cellular energetics, calcium signaling, cell growth and cell differentiation, cell cycle regulation, and cell death. Also, mitochondria are the main sources of intrinsic ROS production. Dysfunction of CSCs mitochondria due to oxidative phosphorylation is reported in several pathological conditions, including metabolic disorders, age-related diseases, and various types of cancers. ROS levels play a significant role in cellular signal transduction and CSCs' identity and differentiation capability. Nrf2 is a master transcription factor that plays critical functions in maintaining cellular redox hemostasis by regulating several antioxidant and detoxification pathways. Recently, the critical function of Nrf2 in CSCs has been revealed by several studies. Nrf2 is an essential molecule in the maintenance of CSCs' stemness and self-renewal in response to different oxidative stresses such as chemotherapy-induced elevation of ROS. Nrf2 enables these cells to recover from chemotherapy damages, and promotes establishment of invasion and dissemination. In this study, we have summarized the role of Nrf2 and mitochondria function CSCs, which promote cancer development. The significant role of Nrf2 in the regulation of mitochondrial function and ROS levels suggests this molecule as a potential target to eradicate CSCs.
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Dzobo K, Senthebane DA, Ganz C, Thomford NE, Wonkam A, Dandara C. Advances in Therapeutic Targeting of Cancer Stem Cells within the Tumor Microenvironment: An Updated Review. Cells 2020; 9:E1896. [PMID: 32823711 PMCID: PMC7464860 DOI: 10.3390/cells9081896] [Citation(s) in RCA: 71] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 08/04/2020] [Accepted: 08/11/2020] [Indexed: 12/24/2022] Open
Abstract
Despite great strides being achieved in improving cancer patients' outcomes through better therapies and combinatorial treatment, several hurdles still remain due to therapy resistance, cancer recurrence and metastasis. Drug resistance culminating in relapse continues to be associated with fatal disease. The cancer stem cell theory posits that tumors are driven by specialized cancer cells called cancer stem cells (CSCs). CSCs are a subpopulation of cancer cells known to be resistant to therapy and cause metastasis. Whilst the debate on whether CSCs are the origins of the primary tumor rages on, CSCs have been further characterized in many cancers with data illustrating that CSCs display great abilities to self-renew, resist therapies due to enhanced epithelial to mesenchymal (EMT) properties, enhanced expression of ATP-binding cassette (ABC) membrane transporters, activation of several survival signaling pathways and increased immune evasion as well as DNA repair mechanisms. CSCs also display great heterogeneity with the consequential lack of specific CSC markers presenting a great challenge to their targeting. In this updated review we revisit CSCs within the tumor microenvironment (TME) and present novel treatment strategies targeting CSCs. These promising strategies include targeting CSCs-specific properties using small molecule inhibitors, immunotherapy, microRNA mediated inhibitors, epigenetic methods as well as targeting CSC niche-microenvironmental factors and differentiation. Lastly, we present recent clinical trials undertaken to try to turn the tide against cancer by targeting CSC-associated drug resistance and metastasis.
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Affiliation(s)
- Kevin Dzobo
- International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component, Wernher and Beit Building (South), UCT Medical Campus, Anzio Road, Observatory, Cape Town 7925, South Africa; (D.A.S.); (C.G.)
- Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa
| | - Dimakatso Alice Senthebane
- International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component, Wernher and Beit Building (South), UCT Medical Campus, Anzio Road, Observatory, Cape Town 7925, South Africa; (D.A.S.); (C.G.)
- Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa
| | - Chelene Ganz
- International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component, Wernher and Beit Building (South), UCT Medical Campus, Anzio Road, Observatory, Cape Town 7925, South Africa; (D.A.S.); (C.G.)
- Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa
| | - Nicholas Ekow Thomford
- Division of Human Genetics, Department of Pathology and Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa; (N.E.T.); (A.W.); (C.D.)
- Department of Medical Biochemistry, School of Medical Sciences, College of Health Sciences, University of Cape Coast, PMB, Cape Coast, Ghana
| | - Ambroise Wonkam
- Division of Human Genetics, Department of Pathology and Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa; (N.E.T.); (A.W.); (C.D.)
| | - Collet Dandara
- Division of Human Genetics, Department of Pathology and Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa; (N.E.T.); (A.W.); (C.D.)
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Walcher L, Kistenmacher AK, Suo H, Kitte R, Dluczek S, Strauß A, Blaudszun AR, Yevsa T, Fricke S, Kossatz-Boehlert U. Cancer Stem Cells-Origins and Biomarkers: Perspectives for Targeted Personalized Therapies. Front Immunol 2020; 11:1280. [PMID: 32849491 PMCID: PMC7426526 DOI: 10.3389/fimmu.2020.01280] [Citation(s) in RCA: 571] [Impact Index Per Article: 114.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Accepted: 05/20/2020] [Indexed: 02/06/2023] Open
Abstract
The use of biomarkers in diagnosis, therapy and prognosis has gained increasing interest over the last decades. In particular, the analysis of biomarkers in cancer patients within the pre- and post-therapeutic period is required to identify several types of cells, which carry a risk for a disease progression and subsequent post-therapeutic relapse. Cancer stem cells (CSCs) are a subpopulation of tumor cells that can drive tumor initiation and can cause relapses. At the time point of tumor initiation, CSCs originate from either differentiated cells or adult tissue resident stem cells. Due to their importance, several biomarkers that characterize CSCs have been identified and correlated to diagnosis, therapy and prognosis. However, CSCs have been shown to display a high plasticity, which changes their phenotypic and functional appearance. Such changes are induced by chemo- and radiotherapeutics as well as senescent tumor cells, which cause alterations in the tumor microenvironment. Induction of senescence causes tumor shrinkage by modulating an anti-tumorigenic environment in which tumor cells undergo growth arrest and immune cells are attracted. Besides these positive effects after therapy, senescence can also have negative effects displayed post-therapeutically. These unfavorable effects can directly promote cancer stemness by increasing CSC plasticity phenotypes, by activating stemness pathways in non-CSCs, as well as by promoting senescence escape and subsequent activation of stemness pathways. At the end, all these effects can lead to tumor relapse and metastasis. This review provides an overview of the most frequently used CSC markers and their implementation as biomarkers by focussing on deadliest solid (lung, stomach, liver, breast and colorectal cancers) and hematological (acute myeloid leukemia, chronic myeloid leukemia) cancers. Furthermore, it gives examples on how the CSC markers might be influenced by therapeutics, such as chemo- and radiotherapy, and the tumor microenvironment. It points out, that it is crucial to identify and monitor residual CSCs, senescent tumor cells, and the pro-tumorigenic senescence-associated secretory phenotype in a therapy follow-up using specific biomarkers. As a future perspective, a targeted immune-mediated strategy using chimeric antigen receptor based approaches for the removal of remaining chemotherapy-resistant cells as well as CSCs in a personalized therapeutic approach are discussed.
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Affiliation(s)
- Lia Walcher
- Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
| | - Ann-Kathrin Kistenmacher
- Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
| | - Huizhen Suo
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Reni Kitte
- Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
| | - Sarah Dluczek
- Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
| | - Alexander Strauß
- Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
| | - André-René Blaudszun
- Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
| | - Tetyana Yevsa
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Stephan Fricke
- Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
| | - Uta Kossatz-Boehlert
- Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
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Rocha Neto JBM, Gomes Neto RJ, Bataglioli RA, Taketa TB, Pimentel SB, Baratti MO, Costa CAR, Carvalho HF, Beppu MM. Engineering the surface of prostate tumor cells and hyaluronan/chitosan multilayer films to modulate cell-substrate adhesion properties. Int J Biol Macromol 2020; 158:197-207. [PMID: 32360468 DOI: 10.1016/j.ijbiomac.2020.04.136] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2020] [Revised: 03/05/2020] [Accepted: 04/18/2020] [Indexed: 12/24/2022]
Abstract
This paper explores different film assembly conditions of the polyelectrolyte solutions of hyaluronan (HA) and chitosan (CHI), as well as both substrate and cell surface modifications, to investigate PC3 cells adhesion properties. UV-Visible, AFM-IR and Zeta potential techniques indicate that the solution ionic strength is a relevant parameter to modulate the free carboxylic groups of HA on the film surface. In addition, capacitive coupling measurements suggest that assembly conditions that favor surface charge mobility inhibit cell adhesion due to polymer rearrangements that support non-specific electrostatic interactions of positively charged CHI residues and the negatively charged cell moieties, rather than specific CD44-hyaluronan interactions. Moreover, the PC3 cells treatment with hyaluronidase and anti-CD44 antibody also highlighted the importance of CD44 binding site availability on the tumor cell adhesion properties. Finally, the conjugation of wheat germ agglutinin on the film surface proved to be a suitable strategy to boost the PC3 cell adhesion properties. Our results reveal the remarkable capacity of HA/CHI films to modulate cell-substrate properties, which pave the road for the development of surfaces suitable for several applications based on biosensing.
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Affiliation(s)
- J B M Rocha Neto
- School of Chemical Engineering, Department of Materials and Bioprocess Engineering, University of Campinas, Campinas 13083-852, São Paulo, Brazil.
| | - R J Gomes Neto
- School of Chemical Engineering, Department of Materials and Bioprocess Engineering, University of Campinas, Campinas 13083-852, São Paulo, Brazil
| | - R A Bataglioli
- School of Chemical Engineering, Department of Materials and Bioprocess Engineering, University of Campinas, Campinas 13083-852, São Paulo, Brazil
| | - T B Taketa
- School of Chemical Engineering, Department of Materials and Bioprocess Engineering, University of Campinas, Campinas 13083-852, São Paulo, Brazil
| | - S B Pimentel
- Institute of Biology, Department of Cell Biology, University of Campinas, Campinas 13083-970, São Paulo, Brazil
| | - M O Baratti
- Institute of Biology, Department of Cell Biology, University of Campinas, Campinas 13083-970, São Paulo, Brazil
| | - C A R Costa
- Brazilian Nanotechnology National Laboratory (LNNano), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas 13083-970, São Paulo, Brazil
| | - H F Carvalho
- Institute of Biology, Department of Cell Biology, University of Campinas, Campinas 13083-970, São Paulo, Brazil
| | - M M Beppu
- School of Chemical Engineering, Department of Materials and Bioprocess Engineering, University of Campinas, Campinas 13083-852, São Paulo, Brazil.
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Zhong W, Pang L, Feng H, Dong H, Wang S, Cong H, Shen Y, Bing Y. Recent advantage of hyaluronic acid for anti-cancer application: a review of "3S" transition approach. Carbohydr Polym 2020; 238:116204. [PMID: 32299556 DOI: 10.1016/j.carbpol.2020.116204] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Revised: 03/06/2020] [Accepted: 03/20/2020] [Indexed: 12/25/2022]
Abstract
In recent years, nano drug delivery system has been widely concerned because of its good therapeutic effect. However, the process from blood circulation to cancer cell release of nanodrugs will be eliminated by the human body's own defense trap, thus reducing the therapeutic effect. In recent years, a "3S" transition concept, including stability transition, surface transition and size transition, was proposed to overcome the barriers in delivery process. Hyaluronic (HA) acid has been widely used in delivery of anticancer drugs due to its excellent biocompatibility, biodegradability and specific targeting to cancer cells. In this paper, the strategies and methods of HA-based nanomaterials using "3S" theory are reviewed. The applications and effects of "3S" modified nanomaterials in various fields are also introduced.
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Affiliation(s)
- Wei Zhong
- Institute of Biomedical Materials and Engineering, College of Materials Science and Engineering, College of Chemistry and Chemical Engineering, Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266071, China
| | - Long Pang
- Institute of Biomedical Materials and Engineering, College of Materials Science and Engineering, College of Chemistry and Chemical Engineering, Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266071, China
| | - Haohui Feng
- Institute of Biomedical Materials and Engineering, College of Materials Science and Engineering, College of Chemistry and Chemical Engineering, Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266071, China
| | - Haonan Dong
- Institute of Biomedical Materials and Engineering, College of Materials Science and Engineering, College of Chemistry and Chemical Engineering, Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266071, China
| | - Song Wang
- Institute of Biomedical Materials and Engineering, College of Materials Science and Engineering, College of Chemistry and Chemical Engineering, Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266071, China
| | - Hailin Cong
- Institute of Biomedical Materials and Engineering, College of Materials Science and Engineering, College of Chemistry and Chemical Engineering, Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266071, China; State Key Laboratory of Bio-Fibers and Eco-Textiles, Qingdao University, Qingdao 266071, China
| | - Youqing Shen
- Institute of Biomedical Materials and Engineering, College of Materials Science and Engineering, College of Chemistry and Chemical Engineering, Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266071, China; Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Center for Bionanoengineering, and Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang, 310027, China
| | - Yu Bing
- Institute of Biomedical Materials and Engineering, College of Materials Science and Engineering, College of Chemistry and Chemical Engineering, Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266071, China; State Key Laboratory of Bio-Fibers and Eco-Textiles, Qingdao University, Qingdao 266071, China.
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Wang J, Liu D, Guan S, Zhu W, Fan L, Zhang Q, Cai D. Hyaluronic acid-modified liposomal honokiol nanocarrier: Enhance anti-metastasis and antitumor efficacy against breast cancer. Carbohydr Polym 2020; 235:115981. [PMID: 32122511 DOI: 10.1016/j.carbpol.2020.115981] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 01/22/2020] [Accepted: 02/10/2020] [Indexed: 12/13/2022]
Abstract
In an effort to enhance antitumor and anti-metastasis of breast cancer, honokiol (HNK) was encapsulated into hyaluronic acid (HA) modified cationic liposomes (Lip). The prepared HA-Lip-HNK had a spherical shape with a narrow size distribution. The enhanced antitumor efficacy of HA-Lip-HNK was investigated in 4T1 cells in vitro, wherein flow cytometry and confocal microscopy analysis revealed its HA/CD44-mediated greater cellular internalization. As anticipate, the significant cytotoxicity of the HA-Lip-HNK was also observed in 4T1 tumor spheroids. Furthermore, the superior prevention of tumor metastasis by HA-Lip-HNK was verified by in vitro anti-invasion, wound healing and anti-migration assessments, and in vivo bioluminescence imaging in pulmonary metastasis model. Finally, compared with unmodified liposomes, the HA-Lip-HNK exhibited higher tumor accumulation, and achieved a tumor growth inhibition rate of 59.5 %. As a result, the HA-Lip-HNK may serve as a promising tumor-targeted drug delivery strategy for the efficient therapy of metastatic breast cancer.
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Affiliation(s)
- Jing Wang
- Institute of Medicine and Drug Research, Qiqihar Medical University, Qiqihar, PR China.
| | - Dan Liu
- Institute of Medicine and Drug Research, Qiqihar Medical University, Qiqihar, PR China.
| | - Shuang Guan
- Institute of Medicine and Drug Research, Qiqihar Medical University, Qiqihar, PR China.
| | - Wenquan Zhu
- College of Pharmacy, Qiqihar Medical University, Qiqihar, PR China.
| | - Li Fan
- Institute of Medicine and Drug Research, Qiqihar Medical University, Qiqihar, PR China.
| | - Qi Zhang
- Institute of Medicine and Drug Research, Qiqihar Medical University, Qiqihar, PR China.
| | - Defu Cai
- Institute of Medicine and Drug Research, Qiqihar Medical University, Qiqihar, PR China.
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40
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Asghari F, Khademi R, Esmaeili Ranjbar F, Veisi Malekshahi Z, Faridi Majidi R. Application of Nanotechnology in Targeting of Cancer Stem Cells: A Review. Int J Stem Cells 2019; 12:227-239. [PMID: 31242721 PMCID: PMC6657943 DOI: 10.15283/ijsc19006] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Revised: 03/15/2019] [Accepted: 04/07/2019] [Indexed: 12/13/2022] Open
Abstract
Cancer is increasingly apparent as a systems-level, network happening. The central tendency of malignant alteration can be described as a two-phase procedure, where an initial increase of network plasticity is followed by reducing plasticity at late stages of tumor improvement. Cancer stem cells (CSCs) are cancer cells that take characteristics associated with normal stem cells. Cancer therapy has been based on the concept that most of the cancer cells have a similar ability to separate metastasise and kill the host. In this review, we addressed the use of nanotechnology in the treatment of cancer stem cells.
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Affiliation(s)
- Fatemeh Asghari
- Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Rahele Khademi
- International affairs, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Faezeh Esmaeili Ranjbar
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Ziba Veisi Malekshahi
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Faridi Majidi
- Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
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Shi L, Wu Z, Miao J, Du S, Ai S, Xu E, Feng M, Song J, Guan W. Adenosine interaction with adenosine receptor A2a promotes gastric cancer metastasis by enhancing PI3K-AKT-mTOR signaling. Mol Biol Cell 2019; 30:2527-2534. [PMID: 31339445 PMCID: PMC6743355 DOI: 10.1091/mbc.e19-03-0136] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
The accumulation of adenosine in the tumor microenvironment is associated with tumor progression in many cancers. However, whether adenosine is involved in gastric cancer (GC) metastasis and progression, and the underlying molecular mechanism, is largely unclear. In this study, we find that GC tissues and cell lines had higher A2aR levels than nontumor gastric tissues and cell lines. A2aR expression correlated positively with TNMstage, and associated with poor outcomes. Adenosine enhanced the expression of the stemness and epithelial-mesenchymal transition-associated genes by binding to A2aR. A2aR expression on GC cells promoted metastasis in vivo. The PI3K-AKT-mTOR signaling pathway was involved in adenosine-stimulated GC cell migration and invasion. Our results indicate that adenosine promotes GC cell invasion and metastasis by interacting with A2aR to enhance PI3K-AKT-mTOR pathway signaling.
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Affiliation(s)
- Linsen Shi
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, People's Republic of China.,The Affiliated Nanjing Drum Tower Clinical College of Nanjing Medical University, Nanjing 210002, People's Republic of China
| | - Zhaoying Wu
- Xuzhou Medical University, Xuzhou 221006, People's Republic of China
| | - Ji Miao
- Department of Gastrointestinal Surgery, The Affiliated Drum Tower Hospital of Nanjing University, Nanjing 210000, People's Republic of China
| | - Shangce Du
- The Affiliated Nanjing Drum Tower Clinical College of Nanjing Medical University, Nanjing 210002, People's Republic of China
| | - Shichao Ai
- Nanjing University, Nanjing 21000, People's Republic of China
| | - En Xu
- Nanjing University, Nanjing 21000, People's Republic of China
| | - Min Feng
- Department of Gastrointestinal Surgery, The Affiliated Drum Tower Hospital of Nanjing University, Nanjing 210000, People's Republic of China
| | - Jun Song
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, People's Republic of China.,Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou 221006, People's Republic of China
| | - Wenxian Guan
- The Affiliated Nanjing Drum Tower Clinical College of Nanjing Medical University, Nanjing 210002, People's Republic of China.,Department of Gastrointestinal Surgery, The Affiliated Drum Tower Hospital of Nanjing University, Nanjing 210000, People's Republic of China
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Multifunctional hyaluronate - nanoparticle hybrid systems for diagnostic, therapeutic and theranostic applications. J Control Release 2019; 303:55-66. [PMID: 30954619 DOI: 10.1016/j.jconrel.2019.04.003] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2018] [Revised: 04/02/2019] [Accepted: 04/03/2019] [Indexed: 12/19/2022]
Abstract
Diagnostic and therapeutic nanoparticles have been actively investigated for the last few decades as new platforms for biomedical applications. Despite their great versatility and potency, nanoparticles have generally required further modification with biocompatible materials such as biopolymers and synthetic polymers for in vivo administration to improve their biological functions, stability, and biocompatibility. Among a variety of natural and synthetic biomaterials, hyaluronate (HA) has been considered a promising biomolecule with which to construct nanohybrid systems, as it can enable long-term and efficient delivery of nanoparticles to target sites as well as physiological stabilization of nanoparticles by forming hydrophilic shells. In this review, we first describe various kinds of HA derivatives and their interactions with nanoparticles, and discuss how to design and develop optimal HA-nanoparticle hybrid systems for biomedical applications. Furthermore, we show several exemplary applications of HA-nanoparticle hybrid systems and provide our perspectives to their futuristic translational applications.
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43
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A comprehensive review of salinomycin derivatives as potent anticancer and anti-CSCs agents. Eur J Med Chem 2019; 166:48-64. [DOI: 10.1016/j.ejmech.2019.01.034] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 01/02/2019] [Accepted: 01/14/2019] [Indexed: 02/08/2023]
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Saw PE, Lee S, Jon S. Naturally Occurring Bioactive Compound‐Derived Nanoparticles for Biomedical Applications. ADVANCED THERAPEUTICS 2019. [DOI: 10.1002/adtp.201800146] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Affiliation(s)
- Phei Er Saw
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene RegulationSun Yat‐Sen Memorial Hospital, Sun Yat‐Sen University Guangzhou 510120 P. R. China
| | - Soyoung Lee
- KAIST Institute for the BioCentury, Department of Biological SciencesKorea Advanced Institute of Science and Technology (KAIST) 291 Daehak‐ro Daejeon 34141 Republic of Korea
| | - Sangyong Jon
- KAIST Institute for the BioCentury, Department of Biological SciencesKorea Advanced Institute of Science and Technology (KAIST) 291 Daehak‐ro Daejeon 34141 Republic of Korea
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45
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Turdo A, Veschi V, Gaggianesi M, Chinnici A, Bianca P, Todaro M, Stassi G. Meeting the Challenge of Targeting Cancer Stem Cells. Front Cell Dev Biol 2019; 7:16. [PMID: 30834247 PMCID: PMC6387961 DOI: 10.3389/fcell.2019.00016] [Citation(s) in RCA: 105] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Accepted: 02/01/2019] [Indexed: 12/18/2022] Open
Abstract
Notwithstanding cancer patients benefit from a plethora of therapeutic alternatives, drug resistance remains a critical hurdle. Indeed, the high mortality rate is associated with metastatic disease, which is mostly incurable due to the refractoriness of metastatic cells to current treatments. Increasing data demonstrate that tumors contain a small subpopulation of cancer stem cells (CSCs) able to establish primary tumor and metastasis. CSCs are endowed with multiple treatment resistance capabilities comprising a highly efficient DNA damage repair machinery, the activation of survival pathways, enhanced cellular plasticity, immune evasion and the adaptation to a hostile microenvironment. Due to the presence of distinct cell populations within a tumor, cancer research has to face the major challenge of targeting the intra-tumoral as well as inter-tumoral heterogeneity. Thus, targeting molecular drivers operating in CSCs, in combination with standard treatments, may improve cancer patients’ outcomes, yielding long-lasting responses. Here, we report a comprehensive overview on the most significant therapeutic advances that have changed the known paradigms of cancer treatment with a particular emphasis on newly developed compounds that selectively affect the CSC population. Specifically, we are focusing on innovative therapeutic approaches including differentiation therapy, anti-angiogenic compounds, immunotherapy and inhibition of epigenetic enzymes and microenvironmental cues.
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Affiliation(s)
- Alice Turdo
- Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy
| | - Veronica Veschi
- Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy
| | - Miriam Gaggianesi
- Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy
| | - Aurora Chinnici
- Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy
| | - Paola Bianca
- Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy
| | - Matilde Todaro
- Department of PROMISE, University of Palermo, Palermo, Italy
| | - Giorgio Stassi
- Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy
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To reduce premature drug release while ensuring burst intracellular drug release of solid lipid nanoparticle-based drug delivery system with clathrin modification. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2019; 15:108-118. [DOI: 10.1016/j.nano.2018.05.014] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Revised: 04/13/2018] [Accepted: 05/20/2018] [Indexed: 12/12/2022]
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Yang W, Zhang H, Xin L. A novel design of HA-coated nanoparticles co-encapsulating plasmid METase and 5-Fu shows enhanced application in targeting gastric cancer stem cells. Biol Chem 2018; 399:293-303. [PMID: 29016350 DOI: 10.1515/hsz-2017-0208] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2017] [Accepted: 09/27/2017] [Indexed: 01/06/2023]
Abstract
Nanoparticles (NPs) are recognized as an attractive vehicles for cancer treatment due to their targeted drug release. Gastric cancer is an important killer disease, and its therapy methods still need improvement. The NPs were prepared using a precipitation method, and were evaluated using transmission electron microscopy (TEM). MTT and Transwell assays were used to determine cell viability and apoptosis. In vivo experiments were performed to validate the effects of NPs on tumor growth. Methioninase (METase)/5-Fu co-encaspulated NPs showed highest ζ size and lowest ζ potential than other NPs. The migration and tumorsphere formation ability of CD44(+) was stronger than CD44(-). The effects of METase/5-Fu co-encaspulated NPs on inhibition cell growth was stronger than that of 5-Fu encaspulated NPs, while HA coated NPs showed significant target ability than that NPs without HA. METase supplementation promoted the inhibition effect of 5-Fu on thymidylate synthetase (TS), as well as cell apoptosis. The in vivo experiments demonstrated that HA coated NPs significantly inhibited tumor growth. It was concluded that HA-coated NPs enhance the target ability, while METase/5-Fu co-encaspulated NPs promote the inhibition effects on tumor growth in gastric cancer.
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Affiliation(s)
- Weifeng Yang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No.1 Minde Road, Donghu District, Nanchang 330006, Jiangxi, China
| | - Houting Zhang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No.1 Minde Road, Donghu District, Nanchang 330006, Jiangxi, China
| | - Lin Xin
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No.1 Minde Road, Donghu District, Nanchang 330006, Jiangxi, China
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Amorim S, da Costa DS, Freitas D, Reis CA, Reis RL, Pashkuleva I, Pires RA. Molecular weight of surface immobilized hyaluronic acid influences CD44-mediated binding of gastric cancer cells. Sci Rep 2018; 8:16058. [PMID: 30375477 PMCID: PMC6207784 DOI: 10.1038/s41598-018-34445-0] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2017] [Accepted: 08/30/2018] [Indexed: 01/02/2023] Open
Abstract
The physiological importance of the interactions between hyaluronic acid (HA) and its main membrane receptor, CD44, in pathological processes, e.g. cancer, is well recognized. However, these interactions are mainly studied in solution, whereas HA in the extracellular matrix (ECM) is partially immobilized via its interactions with other ECM components. We therefore, developed substrates in which HA is presented in an ECM-relevant manner. We immobilized HA with different molecular weights (Mw) in a Layer-by-Layer (LbL) fashion and studied the interactions of the substrates with CD44 and two human gastric cancer cell lines that overexpress this receptor, namely AGS and MKN45. We demonstrate that MKN45 cells are more sensitive to the LbL substrates as compared with AGS. This difference is due to different CD44 expression: while CD44 is detected mainly in the cytoplasm of AGS, MKN45 express CD44 predominantly at the cell membrane where it is involved in the recognition and binding of HA. The invasiveness of the studied cell lines was also evaluated as a function of HA Mw. Invasive profile characterized by low cell adhesion, high cell motility, high expression of cortactin, formation of invadopodia and cell clusters was observed for MKN45 cells when they are in contact with substrates presenting HA of high Mw.
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Affiliation(s)
- Sara Amorim
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal
- ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal
- The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Avepark, 4805-017, Barco, Guimarães, Portugal
| | - Diana Soares da Costa
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal
- ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Daniela Freitas
- Instituto de Investigação e Inovação em Saúde - i3S, Universidade do Porto, Porto, Portugal
- Institute of Molecular Pathology and Immunology of the University of Porto - IPATIMUP, Porto, Portugal
- Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal
| | - Celso A Reis
- Instituto de Investigação e Inovação em Saúde - i3S, Universidade do Porto, Porto, Portugal
- Institute of Molecular Pathology and Immunology of the University of Porto - IPATIMUP, Porto, Portugal
- Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal
- Department of Pathology and Oncology, Faculty of Medicine, Porto University, Porto, Portugal
| | - Rui L Reis
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal
- ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal
- The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Avepark, 4805-017, Barco, Guimarães, Portugal
| | - Iva Pashkuleva
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal.
- ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
| | - Ricardo A Pires
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal.
- ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
- The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Avepark, 4805-017, Barco, Guimarães, Portugal.
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49
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Meran M, Akkus PD, Kurkcuoglu O, Baysak E, Hizal G, Haciosmanoglu E, Unlu A, Karatepe N, Güner FS. Noncovalent Pyrene-Polyethylene Glycol Coatings of Carbon Nanotubes Achieve in Vitro Biocompatibility. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2018; 34:12071-12082. [PMID: 30231197 DOI: 10.1021/acs.langmuir.8b00971] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Single-walled carbon nanotubes (SWNTs) have become increasingly exploited in biological applications, such as imaging and drug delivery. The application of SWNTs in biological settings requires the surface chemistry to remain through the low solubility in aqueous media. In this research, a facile approach for the preparation of a polyethylene glycol (PEG)-coated SWNT-based nanocarrier was reported. We focused on the effect of PEG chain length and SWNT size on the cytotoxicity of PEG-coated SWNTs as a superior drug delivery nanovector. First, all-atom molecular dynamics (MD) simulations were employed to explore the stability and behavior of SWNT/pyrene-PEG (SWNT/Pyr-PEG) structures at a molecular level that is not attainable with experiments. The MD studies revealed that (i) π-π stacking interactions between the pyrene bearing PEG molecules and SWNTs are maintained in bulky situations, regardless of PEG molecular weight or SWNT size; (ii) pyrene molecules diffuse over the SWNT surface without detaching; and (iii) both short and long dynamic Pyr-PEG chains have the capability of effectively coating the SWNT surface. In light of the simulations, noncovalent (π-π stacking) assemblies of SWNT/Pyr-PEG with different molecular weights of PEG ( Mw = 2000, 5000, and 12000) were successfully fabricated and characterized. For longer PEG chains, more effective coating of SWNTs was obtained, resulting in more biocompatible SWNT/Pyr-PEG nanomaterials. The number of SWNTs coated by Pyr-PEG was highly dependent on the length of pyrene bearing PEG polymers. Moreover, the short SWNTs showed a higher amount of PEG coating with respect to the long SWNTs. Cell viability results demonstrated a dose-dependent cytotoxicity of coated SWNTs. Short SWNTs coated with longer PEG chains have low cytotoxicity to be used in in vivo studies.
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Affiliation(s)
- Mehdi Meran
- Department of Chemical Engineering , Istanbul Technical University , 34469 Istanbul , Turkey
| | - Pelin Deniz Akkus
- Department of Chemical Engineering , Istanbul Technical University , 34469 Istanbul , Turkey
| | - Ozge Kurkcuoglu
- Department of Chemical Engineering , Istanbul Technical University , 34469 Istanbul , Turkey
| | - Elif Baysak
- Department of Chemistry , Istanbul Technical University , 34469 Istanbul , Turkey
| | - Gurkan Hizal
- Department of Chemistry , Istanbul Technical University , 34469 Istanbul , Turkey
| | - Ebru Haciosmanoglu
- Department of Physiology, Faculty of Medicine , Istanbul Bilim University , 34394 Istanbul , Turkey
| | - Ayhan Unlu
- Department of Biophysics, Faculty of Medicine , Trakya University , 22030 Edirne , Turkey
| | - Nilgun Karatepe
- Energy Institute, Renewable Energy Division , Istanbul Technical University , 34469 Istanbul , Turkey
| | - F Seniha Güner
- Department of Chemical Engineering , Istanbul Technical University , 34469 Istanbul , Turkey
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50
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Saleem J, Wang L, Chen C. Carbon-Based Nanomaterials for Cancer Therapy via Targeting Tumor Microenvironment. Adv Healthc Mater 2018; 7:e1800525. [PMID: 30073803 DOI: 10.1002/adhm.201800525] [Citation(s) in RCA: 150] [Impact Index Per Article: 21.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Revised: 07/04/2018] [Indexed: 12/12/2022]
Abstract
Cancer remains one of the major health problems all over the world and conventional therapeutic approaches have failed to attain an effective cure. Tumor microenvironments (TME) present a unique challenge in tumor therapy due to their complex structures and multiple components, which also serve as the soil for tumor growth, development, invasion, and migration. The complex TME includes immune cells, fibrous collagen structures, and tortuous blood vessels, in which conventional therapeutic approaches are rendered useless. State-of-the-art nanotechnologies have potential to cope with the threats of malignant tumors. With unique physiochemical properties, carbon nanomaterials (CNMs), including graphene, fullerenes, carbon nanotubes, and carbon quantum dots, offer opportunities to resolve the hurdles, by targeting not only cancer cells but also the TME. This review summarizes the progress about CNM-based cancer therapy strategies, which mainly focuses on both the treatment for cancer cells and TME-targeted modulation. In the last, the challenges for TME-based therapy via CNMs are discussed, which will be important in guiding current basic research to clinical translation in the future.
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Affiliation(s)
- Jabran Saleem
- Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience; National Center for Nanoscience and Technology of China; Beijing 100190 P. R. China
| | - Liming Wang
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety; Institute of High Energy Physics; Chinese Academy of Sciences; Beijing 100049 P. R. China
| | - Chunying Chen
- Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience; National Center for Nanoscience and Technology of China; Beijing 100190 P. R. China
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