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Ghasemi M, Nowroozzadeh MH, Ghorat F, Iraji A, Hashempur MH. Piperine and its nanoformulations: A mechanistic review of their anti-cancer activities. Biomed Pharmacother 2025; 187:118075. [PMID: 40273688 DOI: 10.1016/j.biopha.2025.118075] [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: 12/14/2024] [Revised: 04/08/2025] [Accepted: 04/17/2025] [Indexed: 04/26/2025] Open
Abstract
Piperine, an active compound found in black pepper, exhibits promising anti-cancer properties by targeting critical signaling pathways involved in cancer cell proliferation, migration, and invasion. This review explores the diverse mechanisms through which piperine exerts its effects, including inhibition of the PI3K/Akt/mTOR and ERK1/2 pathways, activation of p38 and JNK pathways, and suppression of NF-kB/AP-1 signaling. Piperine disrupts Wnt/β-catenin signaling by inhibiting β-catenin nuclear translocation and TCF binding, thereby impairing cancer cell growth and metastasis. Additionally, piperine demonstrates anti-inflammatory actions by reducing CXCL8 expression and modulating the p38 MAPK and JNK pathways. To overcome the issues of low solubility and bioavailability, several nanoformulations of piperinewere developed, such as polymer nanoparticles, nanoemulsion, liposomes, micelles, metal-organic frameworks and inorganic carriers, establishing promising cytotoxicity, prolonged-release, enhanced cellular influx, and directed drug delivery. The mechanisms involve G₀ and G₂/M arrest of the cell cycle, mitochondria-mediated apoptosis (involving Bax/Bcl-2 modulation and caspase activation), and cancer celldeath. In vivo studies underscore the efficacy of piperine, while synergistic effects with other natural products and chemotherapy highlight its potential as a versatile therapeutic agent as an anticancer agent. These findings underscore piperine's potential as a multifaceted therapeutic agent for cancer treatment, emphasizing its diverse mechanisms of action and promising role in oncology.
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Affiliation(s)
- Mahshad Ghasemi
- Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - M Hossein Nowroozzadeh
- Poostchi Ophthalmology Research Center, Department of Ophthalmology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Fereshteh Ghorat
- Non-Communicable Diseases Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Aida Iraji
- Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Mohammad Hashem Hashempur
- Research Center for Traditional Medicine and History of Medicine, Department of Persian Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
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2
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Ni CX, Xu JJ, Pang Y, Xu JJ. Treatment strategies targeting the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin pathway against triple-negative breast cancer. World J Clin Oncol 2025; 16:104623. [DOI: 10.5306/wjco.v16.i5.104623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Revised: 02/25/2025] [Accepted: 03/25/2025] [Indexed: 05/19/2025] Open
Abstract
Triple negative breast cancer (TNBC) is an exceptionally aggressive subtype of breast cancer with a poor prognosis. TNBC patients have limited treatment options beyond conventional chemotherapy, and they face significant challenges associated with disease recurrence and resistance to chemotherapy. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway plays a pivotal role in cell proliferation, growth, metabolism, and survival. Its aberrant activation is closely linked to the development and progression of TNBC, as well as treatment response and drug resistance. Currently, numerous targeted drugs specifically inhibiting this signaling pathway are being developed and undergoing clinical trials. These include inhibitors targeting PI3K, AKT, or mTOR individually, as well as dual-target or multi-target inhibitors simultaneously targeting different components of this pathway. Encouragingly, some inhibitors have demonstrated promising potential in clinical trials. This review delves into the therapeutic potential of the PI3K/AKT/mTOR signaling pathway for TNBC and explores prospects for drug discovery.
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Affiliation(s)
- Chun-Xiao Ni
- Department of Minimally Invasive Oncology, Tai’an Central Hospital Affiliated to Qingdao University, Tai’an 271000, Shandong Province, China
| | - Jia-Ju Xu
- Department of Pediatrics, Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai 264000, Shandong Province, China
| | - Yu Pang
- Department of Pathology, Tai’an Central Hospital Affiliated to Qingdao University, Tai’an 271000, Shandong Province, China
| | - Jia-Ju Xu
- Department of Medical Oncology, Tai’an Central Hospital Affiliated to Qingdao University, Tai’an 271000, Shandong Province, China
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Dechbumroong P, Hu R, Keaswejjareansuk W, Namdee K, Liang XJ. Recent advanced lipid-based nanomedicines for overcoming cancer resistance. CANCER DRUG RESISTANCE (ALHAMBRA, CALIF.) 2024; 7:24. [PMID: 39050885 PMCID: PMC11267154 DOI: 10.20517/cdr.2024.19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Revised: 06/09/2024] [Accepted: 06/17/2024] [Indexed: 07/27/2024]
Abstract
The increasing prevalence of cancer drug resistance not only critically limits the efficiency of traditional therapies but also causes relapses or recurrences of cancer. Consequently, there remains an urgent need to address the intricate landscape of drug resistance beyond traditional cancer therapies. Recently, nanotechnology has played an important role in the field of various drug delivery systems for the treatment of cancer, especially therapy-resistant cancer. Among advanced nanomedicine technologies, lipid-based nanomaterials have emerged as effective drug carriers for cancer treatment, significantly improving therapeutic effects. Due to their biocompatibility, simplicity of preparation, and potential for functionalization, lipid-based nanomaterials are considered powerful competitors for resistant cancer. In this review, an overview of lipid-based nanomaterials for addressing cancer resistance is discussed. We summarize the recent progress in overcoming drug resistance in cancer by these lipid-based nanomaterials, and highlight their potential in future applications to reverse cancer resistance.
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Affiliation(s)
- Piroonrat Dechbumroong
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100049, China
- School of Nanoscience and Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
- National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency, Pathum Thani 12120, Thailand
- Authors contributed equally
| | - Runjing Hu
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100049, China
- School of Nanoscience and Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
- Authors contributed equally
| | - Wisawat Keaswejjareansuk
- National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency, Pathum Thani 12120, Thailand
| | - Katawut Namdee
- National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency, Pathum Thani 12120, Thailand
| | - Xing-Jie Liang
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100049, China
- School of Nanoscience and Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
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Priya V, Samridhi, Singh N, Dash D, Muthu MS. Nattokinase Encapsulated Nanomedicine for Targeted Thrombolysis: Development, Improved in Vivo Thrombolytic Effects, and Ultrasound/Photoacoustic Imaging. Mol Pharm 2024; 21:283-302. [PMID: 38126777 DOI: 10.1021/acs.molpharmaceut.3c00830] [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] [Indexed: 12/23/2023]
Abstract
Nattokinase (NK), a potent thrombolytic enzyme that dissolves blood clots, is highly used in the treatment of cardiovascular disorders. However, its effective delivery remains demanding because of stability and bioavailability problems owing to its high molecular weight and proteineous nature. In this research, we have developed novel NK-loaded nontargeted liposomes (NK-LS) and targeted liposomes (RGD-NK-LS and AM-NK-LS) by the reverse phase evaporation method. The physiochemical characterizations (particle size, polydispersity index, zeta potential, and morphology) were performed by a Zetasizer, SEM, TEM, and AFM. The Bradford assay and XPS analysis confirmed the successful surface conjugation of the targeting ligands. Platelet interaction studies by CLSM, photon imager optima, and flow cytometry showed significantly higher (P < 0.05) platelet binding affinity of targeted liposomes. In vitro evaluations were performed using human blood and a fibrinolysis study by CLSM imaging demonstrating the potent antithrombotic efficacy of AM-NK-LS. Furthermore, bleeding and clotting time studies revealed that the targeted liposomes were free from any bleeding complications. Moreover, the in vivo FeCl3 model on Sprague-Dawley (SD) rats using a Doppler flow meter and ultrasound/photoacoustic imaging indicated the increased % thrombolysis and potent affinity of targeted liposomes toward the thrombus site. Additionally, in vitro hemocompatibility and histopathology studies demonstrated the safety and biocompatibility of the nanoformulations.
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Affiliation(s)
- Vishnu Priya
- Department of Pharmaceutical Engineering and Technology, IIT (BHU), Varanasi 221005, U.P., India
| | - Samridhi
- Department of Pharmaceutical Engineering and Technology, IIT (BHU), Varanasi 221005, U.P., India
| | - Nitesh Singh
- Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, U.P., India
| | - Debabrata Dash
- Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, U.P., India
| | - Madaswamy S Muthu
- Department of Pharmaceutical Engineering and Technology, IIT (BHU), Varanasi 221005, U.P., India
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5
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Kumari L, Mishra L, Patel P, Sharma N, Gupta GD, Kurmi BD. Emerging targeted therapeutic strategies for the treatment of triple-negative breast cancer. J Drug Target 2023; 31:889-907. [PMID: 37539789 DOI: 10.1080/1061186x.2023.2245579] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 07/30/2023] [Indexed: 08/05/2023]
Abstract
Triple-negative breast cancer (TNBC), a subtype of breast cancer that lacks expression of oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2), has clinical features including a high degree of invasiveness, an elevated risk of metastasis, tendency to relapse, and poor prognosis. It constitutes around 10-15% of all breast cancer, and having heredity of BRCA1 mutated breast cancer could be a reason for the occurrence of TNBC in women. Overexpression of cellular and molecular targets, i.e. CD44 receptor, EGFR receptor, Folate receptor, Transferrin receptor, VEGF receptor, and Androgen receptor, have emerged as promising targets for treating TNBC. Signalling pathways such as Notch signalling and PI3K/AKT/mTOR also play a significant role in carrying out and managing crucial pro-survival and pro-growth cellular processes that can be utilised for targeted therapy against triple-negative breast cancer. This review sheds light on various targeting strategies, including cellular and molecular targets, signalling pathways, poly (ADP-ribose) polymerase inhibitors, antibody-drug conjugates, and immune checkpoint inhibitors PARP, immunotherapy, ADCs have all found a place in the current TNBC therapeutic paradigm. The role of photothermal therapy (PTT) and photodynamic therapy (PDT) has also been explored briefly.
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Affiliation(s)
- Lakshmi Kumari
- Department of Pharmaceutics, ISF College Pharmacy, Moga, Punjab, India
| | - Lopamudra Mishra
- Department of Pharmaceutics, ISF College Pharmacy, Moga, Punjab, India
| | - Preeti Patel
- Department of Pharmaceutical Chemistry, ISF College Pharmacy, Moga, Punjab, India
| | - Nitin Sharma
- Department of Pharmaceutics, ISF College Pharmacy, Moga, Punjab, India
| | | | - Balak Das Kurmi
- Department of Pharmaceutics, ISF College Pharmacy, Moga, Punjab, India
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6
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Zou J. Site-specific delivery of cisplatin and paclitaxel mediated by liposomes: A promising approach in cancer chemotherapy. ENVIRONMENTAL RESEARCH 2023; 238:117111. [PMID: 37734579 DOI: 10.1016/j.envres.2023.117111] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/25/2023] [Accepted: 09/09/2023] [Indexed: 09/23/2023]
Abstract
The site-specific delivery of drugs, especially anti-cancer drugs has been an interesting field for researchers and the reason is low accumulation of cytotoxic drugs in cancer cells. Although combination cancer therapy has been beneficial in providing cancer drug sensitivity, targeted delivery of drugs appears to be more efficient. One of the safe, biocompatible and efficient nano-scale delivery systems in anti-cancer drug delivery is liposomes. Their particle size is small and they have other properties such as adjustable physico-chemical properties, ease of functionalization and high entrapment efficiency. Cisplatin is a chemotherapy drug with clinical approval in patients, but its accumulation in cancer cells is low due to lack of targeted delivery and repeated administration results in resistance development. Gene and drug co-administration along with cisplatin/paclitaxel have resulted in increased sensitivity in tumor cells, but there is still space for more progress in cancer therapy. The delivery of cisplatin/paclitaxel by liposomes increases accumulation of drug in tumor cells and impairs activity of efflux pumps in promoting cytotoxicity. Moreover, phototherapy along with cisplatin/paclitaxel delivery can increase potential in tumor suppression. Smart nanoparticles including pH-sensitive nanoparticles provide site-specific delivery of cisplatin/paclitaxel. The functionalization of liposomes can be performed by ligands to increase targetability towards tumor cells in mediating site-specific delivery of cisplatin/paclitaxel. Finally, liposomes can mediate co-delivery of cisplatin/paclitaxel with drugs or genes in potentiating tumor suppression. Since drug resistance has caused therapy failure in cancer patients, and cisplatin/paclitaxel are among popular chemotherapy drugs, delivery of these drugs mediates targeted suppression of cancers and prevents development of drug resistance. Because of biocompatibility and safety of liposomes, they are currently used in clinical trials for treatment of cancer patients. In future, the optimal dose of using liposomes and optimal concentration of loading cisplatin/paclitaxel on liposomal nanocarriers in clinical trials should be determined.
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Affiliation(s)
- Jianyong Zou
- Department of Thoracic Surgery, The first Affiliated Hospital of Sun Yat-Sen University, 510080, Guangzhou, PR China.
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7
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Xu W, Xiao Y, Zheng L, Xu M, Jiang X, Wang L. Enhancing Paclitaxel Efficacy with Piperine-Paclitaxel Albumin Nanoparticles in Multidrug-Resistant Triple-Negative Breast Cancer by Inhibiting P-Glycoprotein. Pharmaceutics 2023; 15:2703. [PMID: 38140044 PMCID: PMC10747290 DOI: 10.3390/pharmaceutics15122703] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Revised: 11/24/2023] [Accepted: 11/26/2023] [Indexed: 12/24/2023] Open
Abstract
Triple-negative breast cancer (TNBC) is a highly aggressive disease with rapid progression and poor prognosis due to multidrug resistance (MDR). Piperine (PIP) shows promise as a P-gp inhibitor, capable of sensitizing chemotherapeutic drugs and exhibiting antitumor properties. This study explores the inhibitory mechanism of PIP on P-glycoprotein (P-gp) and its capacity to enhance the sensitivity of paclitaxel (PTX). We subsequently evaluated the efficacy and safety of albumin nanoparticles that co-encapsulate PTX and PIP (PP@AN). The results demonstrated that PIP enhanced the accumulation of PTX intracellularly, as determined with HPLC/MS/MS analysis. PIP was also found to increase cell sensitivity to PTX. Furthermore, we explored the inhibitory mechanism of PIP on P-gp, utilizing molecular docking simulations, RT-qPCR, and Western blot analysis. PIP appears to compete with the active paclitaxel binding site on P-gp, affecting ATPase activity and downregulating the MDR1 gene and P-gp expression. In summary, PIP could inhibit P-gp and act as a sensitizer in the treatment of TNBC with PTX. Moreover, stable and uniform PP@AN was successfully formulated, resulting in a significant increase in drug accumulation within cells as well as the downregulation of P-gp in tumors at the optimal ratio (PTX:PIP = 1:2). This led to an improvement in the antitumor effect in vivo while also reducing hepatotoxicity and hemototoxicity following chemotherapy. This study comprehensively investigated PIP's inhibitory effect and mechanism on P-gp. We present a new approach for co-delivering PIP and PTX using albumin nanoparticles, which reduced toxicity and improved therapeutic efficacy both in vivo and in vitro.
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Affiliation(s)
- Wenwen Xu
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Department of Clinical Pharmacy and Pharmacy Administration, West China School of Pharmacy, Sichuan University, Chengdu 610064, China; (W.X.); (Y.X.); (M.X.); (X.J.)
| | - Yumeng Xiao
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Department of Clinical Pharmacy and Pharmacy Administration, West China School of Pharmacy, Sichuan University, Chengdu 610064, China; (W.X.); (Y.X.); (M.X.); (X.J.)
| | - Liang Zheng
- Department of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China;
| | - Mingyu Xu
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Department of Clinical Pharmacy and Pharmacy Administration, West China School of Pharmacy, Sichuan University, Chengdu 610064, China; (W.X.); (Y.X.); (M.X.); (X.J.)
| | - Xuehua Jiang
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Department of Clinical Pharmacy and Pharmacy Administration, West China School of Pharmacy, Sichuan University, Chengdu 610064, China; (W.X.); (Y.X.); (M.X.); (X.J.)
| | - Ling Wang
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Department of Clinical Pharmacy and Pharmacy Administration, West China School of Pharmacy, Sichuan University, Chengdu 610064, China; (W.X.); (Y.X.); (M.X.); (X.J.)
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8
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Fatima Qizilbash F, Sartaj A, Qamar Z, Kumar S, Imran M, Mohammed Y, Ali J, Baboota S, Ali A. Nanotechnology revolutionises breast cancer treatment: harnessing lipid-based nanocarriers to combat cancer cells. J Drug Target 2023; 31:794-816. [PMID: 37525966 DOI: 10.1080/1061186x.2023.2243403] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 07/21/2023] [Accepted: 07/26/2023] [Indexed: 08/02/2023]
Abstract
One of the most common cancers that occur in females is breast cancer. Despite the significant leaps and bounds that have been made in treatment of breast cancer, the disease remains one of the leading causes of death among women and a major public health challenge. The therapeutic efficacy of chemotherapeutics is hindered by chemoresistance and toxicity. Nano-based lipid drug delivery systems offer controlled drug release, nanometric size and site-specific targeting. Breast cancer treatment includes surgery, chemotherapy and radiotherapy. Despite this, no single method of treatment for the condition is currently effective due to cancer stem cell metastasis and chemo-resistance. Therefore, the employment of nanocarrier systems is necessary in order to target breast cancer stem cells. This article addresses breast cancer treatment options, including modern treatment procedures such as chemotherapy, etc. and some innovative therapeutic options highlighting the role of lipidic nanocarriers loaded with chemotherapeutic drugs such as nanoemulsion, solid-lipid nanoparticles, nanostructured lipid carriers and liposomes, and their investigations have demonstrated that they can limit cancer cell growth, reduce the risk of recurrence, as well as minimise post-chemotherapy metastasis. This article also explores FDA-approved lipid-based nanocarriers, commercially available formulations, and ligand-based formulations that are being considered for further research.
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Affiliation(s)
| | - Ali Sartaj
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, New Delhi, India
- Lloyd School of Pharmacy, Greater Noida, India
| | - Zufika Qamar
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, New Delhi, India
| | - Shobhit Kumar
- Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology (MIET), Meerut, India
| | - Mohammad Imran
- Therapeutics Research Group, Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, Australia
| | - Yousuf Mohammed
- Therapeutics Research Group, Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, Australia
- School of Pharmacy, The University of Queensland, Brisbane, Australia
| | - Javed Ali
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, New Delhi, India
| | - Sanjula Baboota
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, New Delhi, India
| | - Asgar Ali
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, New Delhi, India
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Ramos INDF, da Silva MF, Lopes JMS, Cruz JN, Alves FS, do Rego JDAR, Costa MLD, Assumpção PPD, Barros Brasil DDS, Khayat AS. Extraction, Characterization, and Evaluation of the Cytotoxic Activity of Piperine in Its Isolated form and in Combination with Chemotherapeutics against Gastric Cancer. Molecules 2023; 28:5587. [PMID: 37513459 PMCID: PMC10385350 DOI: 10.3390/molecules28145587] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Revised: 06/30/2023] [Accepted: 07/05/2023] [Indexed: 07/30/2023] Open
Abstract
Gastric cancer is one of the most frequent types of neoplasms worldwide, usually presenting as aggressive and difficult-to-manage tumors. The search for new structures with anticancer potential encompasses a vast research field in which natural products arise as promising alternatives. In this scenario, piperine, an alkaloid of the Piper species, has received attention due to its biological activity, including anticancer attributes. The present work proposes three heating-independent, reliable, low-cost, and selective methods for obtaining piperine from Piper nigrum L. (Black pepper). Electronic (SEM) and optical microscopies, X-ray diffraction, nuclear magnetic resonance spectroscopies (13C and 1H NMR), and optical spectroscopies (UV-Vis, photoluminescence, and FTIR) confirm the obtention of piperine crystals. The MTT assay reveals that the piperine samples exhibit good cytotoxic activity against primary and metastasis models of gastric cancer cell lines from the Brazilian Amazon. The samples showed selective cytotoxicity on the evaluated models, revealing higher effectiveness in cells bearing a higher degree of aggressiveness. Moreover, the investigated piperine crystals demonstrated the ability to act as a good cytotoxicity enhancer when combined with traditional chemotherapeutics (5-FU and GEM), allowing the drugs to achieve the same cytotoxic effect in cells employing lower concentrations. These results establish piperine as a promising molecule for therapy investigations in aggressive gastric cancer, both in its isolated form or as a bioenhancer.
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Affiliation(s)
| | | | | | - Jordy Neves Cruz
- Institute of Technology, Federal University of Pará, Belém 66075-110, PA, Brazil
| | - Fabrine Silva Alves
- Graduate Program in Pharmaceutical Innovation, Federal University of Pará, Belém 66075-110, PA, Brazil
| | | | | | | | - Davi do Socorro Barros Brasil
- Institute of Technology, Federal University of Pará, Belém 66075-110, PA, Brazil
- Graduate Program in Pharmaceutical Innovation, Federal University of Pará, Belém 66075-110, PA, Brazil
- Graduate Program in Science and Environment, Federal University of Pará, Belém 66075-110, PA, Brazil
| | - André Salim Khayat
- Oncology Research Center, Federal University of Pará, Belém 66075-110, PA, Brazil
- Institute of Biological Science, Federal University of Pará, Belém 66075-110, PA, Brazil
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10
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Mehata AK, Singh V, Singh N, Mandal A, Dash D, Koch B, Muthu MS. Chitosan- g-estrone Nanoparticles of Palbociclib Vanished Hypoxic Breast Tumor after Targeted Delivery: Development and Ultrasound/Photoacoustic Imaging. ACS APPLIED MATERIALS & INTERFACES 2023. [PMID: 37433149 DOI: 10.1021/acsami.3c03184] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/13/2023]
Abstract
Breast cancer is the leading cause of death among women globally. Approximately 80% of all breast cancers diagnosed are overexpressed with estrogen receptors (ERs). In this study, we have developed an estrone (Egen)-grafted chitosan-based polymeric nanocarrier for the targeted delivery of palbociclib (PLB) to breast cancer. The nanoparticles (NPs) were prepared by solvent evaporation using the ionic gelation method and characterized for particle size, zeta potential, polydispersity, surface morphology, surface chemistry, drug entrapment efficiency, cytotoxicity assay, cellular uptake, and apoptosis study. The developed PLB-CS NPs and PLB-CS-g-Egen NPs had a particle size of 116.3 ± 1.53 nm and 141.6 ± 1.97 nm, respectively. The zeta potential of PLB-CS NPs and PLB-CS-g-Egen NPs was found to be 18.70 ± 0.416 mV and 12.45 ± 0.574 mV, respectively. The morphological analysis demonstrated that all NPs were spherical in shape and had a smooth surface. An in vitro cytotoxicity assay was performed in estrogen receptor (ER)-expressing MCF7 cells and T47D cells, which suggested that targeted NPs were 57.34- and 30.32-fold more cytotoxic compared to the pure PLB, respectively. Additionally, cell cycle analysis confirmed that cell cycle progression from the G1 into S phase was blocked more efficiently by targeted NPs compared to nontargeted NPs and PLB in MCF7 cells. In vivo pharmacokinetic studies demonstrated that entrapment of the PLB in the NPs improved the half-life and bioavailability by ∼2-3-fold. Further, ultrasound and photoacoustic imaging of DMBA induced breast cancer in the Sprague-Dawley (SD) rat showed that targeted NPs completely vanished breast tumor, reduced hypoxic tumor volume, and suppressed tumor angiogenesis more efficiently compared to the nontargeted NPs and free PLB. Further, in vitro hemocompatibility and histopathology studies suggested that NPs were biocompatible and safe for clinical use.
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Affiliation(s)
- Abhishesh Kumar Mehata
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology, (BHU), Varanasi 221005, Uttar Pradesh, India
| | - Virendra Singh
- Cancer Biology Laboratory, Department of Zoology Institute of Science, (BHU), Varanasi 221005, Uttar Pradesh, India
| | - Nitesh Singh
- Department of Biochemistry, Institute of Medical Sciences, (BHU), Varanasi 221005, Uttar Pradesh, India
| | - Abhijit Mandal
- Department of Radiotherapy and Radiation Medicine, Institute of Medical Sciences, (BHU), Varanasi 221005, Uttar Pradesh, India
| | - Debabrata Dash
- Department of Biochemistry, Institute of Medical Sciences, (BHU), Varanasi 221005, Uttar Pradesh, India
| | - Biplob Koch
- Cancer Biology Laboratory, Department of Zoology Institute of Science, (BHU), Varanasi 221005, Uttar Pradesh, India
| | - Madaswamy S Muthu
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology, (BHU), Varanasi 221005, Uttar Pradesh, India
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11
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Chaudhuri A, Kumar DN, Dehari D, Patil R, Singh S, Kumar D, Agrawal AK. Endorsement of TNBC Biomarkers in Precision Therapy by Nanotechnology. Cancers (Basel) 2023; 15:cancers15092661. [PMID: 37174125 PMCID: PMC10177107 DOI: 10.3390/cancers15092661] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 05/05/2023] [Accepted: 05/06/2023] [Indexed: 05/15/2023] Open
Abstract
Breast cancer is a heterogeneous disease which accounts globally for approximately 1 million new cases annually, wherein more than 200,000 of these cases turn out to be cases of triple-negative breast cancer (TNBC). TNBC is an aggressive and rare breast cancer subtype that accounts for 10-15% of all breast cancer cases. Chemotherapy remains the only therapy regimen against TNBC. However, the emergence of innate or acquired chemoresistance has hindered the chemotherapy used to treat TNBC. The data obtained from molecular technologies have recognized TNBC with various gene profiling and mutation settings that have helped establish and develop targeted therapies. New therapeutic strategies based on the targeted delivery of therapeutics have relied on the application of biomarkers derived from the molecular profiling of TNBC patients. Several biomarkers have been found that are targets for the precision therapy in TNBC, such as EGFR, VGFR, TP53, interleukins, insulin-like growth factor binding proteins, c-MET, androgen receptor, BRCA1, glucocorticoid, PTEN, ALDH1, etc. This review discusses the various candidate biomarkers identified in the treatment of TNBC along with the evidence supporting their use. It was established that nanoparticles had been considered a multifunctional system for delivering therapeutics to target sites with increased precision. Here, we also discuss the role of biomarkers in nanotechnology translation in TNBC therapy and management.
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Affiliation(s)
- Aiswarya Chaudhuri
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi 221005, India
| | - Dulla Naveen Kumar
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi 221005, India
| | - Deepa Dehari
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi 221005, India
| | - Rohit Patil
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi 221005, India
| | - Sanjay Singh
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi 221005, India
- Department of Pharmaceutics, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya Vihar, Raebareli Road, Lucknow 226025, India
| | - Dinesh Kumar
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi 221005, India
| | - Ashish Kumar Agrawal
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi 221005, India
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12
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Marques AC, Costa PC, Velho S, Amaral MH. Lipid Nanoparticles Functionalized with Antibodies for Anticancer Drug Therapy. Pharmaceutics 2023; 15:216. [PMID: 36678845 PMCID: PMC9864942 DOI: 10.3390/pharmaceutics15010216] [Citation(s) in RCA: 39] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 12/31/2022] [Accepted: 01/05/2023] [Indexed: 01/11/2023] Open
Abstract
Nanotechnology takes the lead in providing new therapeutic options for cancer patients. In the last decades, lipid-based nanoparticles-solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), liposomes, and lipid-polymer hybrid nanoparticles-have received particular interest in anticancer drug delivery to solid tumors. To improve selectivity for target cells and, thus, therapeutic efficacy, lipid nanoparticles have been functionalized with antibodies that bind to receptors overexpressed in angiogenic endothelial cells or cancer cells. Most papers dealing with the preclinical results of antibody-conjugated nanoparticles claim low systemic toxicity and effective tumor inhibition, which have not been successfully translated into clinical use yet. This review aims to summarize the current "state-of-the-art" in anticancer drug delivery using antibody-functionalized lipid-based nanoparticles. It includes an update on promising candidates that entered clinical trials and some explanations for low translation success.
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Affiliation(s)
- Ana Camila Marques
- UCIBIO—Applied Molecular Biosciences Unit, MEDTECH, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
- Associate Laboratory i4HB—Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
| | - Paulo C. Costa
- UCIBIO—Applied Molecular Biosciences Unit, MEDTECH, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
- Associate Laboratory i4HB—Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
| | - Sérgia Velho
- i3S—Instituto de Investigação e Inovação em Saúde, University of Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal
- IPATIMUP—Institute of Molecular Pathology and Immunology of the University of Porto, R. Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal
| | - Maria Helena Amaral
- UCIBIO—Applied Molecular Biosciences Unit, MEDTECH, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
- Associate Laboratory i4HB—Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
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13
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Priya V, Singh SK, Revand R, Kumar S, Mehata AK, Sushmitha P, Mahto SK, Muthu MS. GPIIb/IIIa Receptor Targeted Rutin Loaded Liposomes for Site-Specific Antithrombotic Effect. Mol Pharm 2023; 20:663-679. [PMID: 36413707 DOI: 10.1021/acs.molpharmaceut.2c00848] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Rutin (RUT) is a flavonoid obtained from a natural source and is reported for antithrombotic potential, but its delivery remains challenging because of its poor solubility and bioavailability. In this research, we have fabricated novel rutin loaded liposomes (RUT-LIPO, nontargeted), liposomes conjugated with RGD peptide (RGD-RUT-LIPO, targeted), and abciximab (ABX-RUT-LIPO, targeted) by ethanol injection method. The particle size, ζ potential, and morphology of prepared liposomes were analyzed by using DLS, SEM, and TEM techniques. The conjugation of targeting moiety on the surface of targeted liposomes was confirmed by XPS analysis and Bradford assay. In vitro assessment such as blood clot assay, aPTT assay, PT assay, and platelet aggregation analysis was performed using human blood which showed the superior antithrombotic potential of ABX-RUT-LIPO and RGD-RUT-LIPO liposomes. The clot targeting efficiency was evaluated by in vitro imaging and confocal laser scanning microscopy. A significant (P < 0.05) rise in the affinity of targeted liposomes toward activated platelets was demonstrated that revealed their remarkable potential in inhibiting thrombus formation. Furthermore, an in vivo study executed on Sprague Dawley rats (FeCl3 model) demonstrated improved antithrombotic activity of RGD-RUT-LIPO and ABX-RUT-LIPO compared with pure drug. The pharmacokinetic study performed on rats demonstrates the increase in bioavailability when administered as liposomal formulation as compared to RUT. Moreover, the tail bleeding assay and clotting time study (Swiss Albino mice) indicated a better antithrombotic efficacy of targeted liposomes than control preparations. Additionally, biocompatibility of liposomal formulations was determined by an in vitro hemolysis study and cytotoxicity assay, which showed that they were hemocompatible and safe for human use. A histopathology study on rats suggested no severe toxicity of prepared liposomal formulations. Thus, RUT encapsulated nontargeted and targeted liposomes exhibited superior antithrombotic potential over RUT and could be used as a promising carrier for future use.
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Affiliation(s)
- Vishnu Priya
- Department of Pharmaceutical Engineering and Technology, IIT (BHU), Varanasi221005, UP, India
| | - Sanjeev K Singh
- Department of Physiology, IMS, Banaras Hindu University, Varanasi221005, India
| | - Ravindran Revand
- Department of Physiology, IMS, Banaras Hindu University, Varanasi221005, India
| | - Sandip Kumar
- Department of Pathology, IMS, Banaras Hindu University, Varanasi221005, India
| | - Abhishesh Kumar Mehata
- Department of Pharmaceutical Engineering and Technology, IIT (BHU), Varanasi221005, UP, India
| | - Paulraj Sushmitha
- School of Biomedical Engineering, IIT (BHU), Varanasi221005, UPIndia
| | | | - Madaswamy S Muthu
- Department of Pharmaceutical Engineering and Technology, IIT (BHU), Varanasi221005, UP, India
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14
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Vikas, Mehata AK, Suseela MNL, Behera C, Kumari P, Mahto SK, Muthu MS. Chitosan-alginate nanoparticles of cabazitaxel: Design, dual-receptor targeting and efficacy in lung cancer model. Int J Biol Macromol 2022; 221:874-890. [PMID: 36089091 DOI: 10.1016/j.ijbiomac.2022.09.053] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 08/30/2022] [Accepted: 09/06/2022] [Indexed: 11/05/2022]
Abstract
Cabazitaxel (CZT) loaded chitosan-alginate based (CSA) nanoparticles were developed with dual targeting functions of both folate receptor and epidermal growth factor receptor (EGFR) using ionic gelation technique. The chitosan-folate conjugate was synthesized, and characterized by using FTIR, NMR and Mass spectroscopy. The physicochemical parameters and morphology of all CSA nanoparticles were examined. The degree of conjugation of folic acid and cetuximab (CTXmab) was determined by UV-Visible spectroscopy and Bradford assay, respectively. Moreover, XPS analysis also supported the presence of the ligands on nanoparticles. The cellular-uptake study performed on A-549 cells demonstrated a significant enhancement in the uptake of dual-receptor targeted CSA nanoparticles than non-targeted and single-receptor targeted CSA nanoparticles. Further, CZT-loaded dual receptors targeted CSA nanoparticles also showed significantly lower IC50 values (~38 folds) than the CZT control against A-549 cells. Further, in-vivo histopathological evaluations of dual receptor-targeted CSA nanoparticles have demonstrated better safety in Wistar rats. Moreover, its treatment on the Benzo(a)pyrene (B(a)P) induced lung cancer mice model has showed the enhanced anticancer efficacy of CZT with a prolonged survival rate.
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Affiliation(s)
- Vikas
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi 221005, UP, India
| | - Abhishesh Kumar Mehata
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi 221005, UP, India
| | - M Nikitha Lakshmi Suseela
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi 221005, UP, India
| | - Chittaranjan Behera
- PK-PD Tox & Formulation Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India
| | - Pooja Kumari
- School of Biomedical Engineering, Indian Institute of Technology (BHU), Varanasi 221005, UP, India
| | - Sanjeev Kumar Mahto
- School of Biomedical Engineering, Indian Institute of Technology (BHU), Varanasi 221005, UP, India
| | - Madaswamy S Muthu
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi 221005, UP, India.
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15
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Rethi L, Mutalik C, Anurogo D, Lu LS, Chu HY, Yougbaré S, Kuo TR, Cheng TM, Chen FL. Lipid-Based Nanomaterials for Drug Delivery Systems in Breast Cancer Therapy. NANOMATERIALS (BASEL, SWITZERLAND) 2022; 12:2948. [PMID: 36079985 PMCID: PMC9458017 DOI: 10.3390/nano12172948] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 08/18/2022] [Accepted: 08/23/2022] [Indexed: 06/15/2023]
Abstract
Globally, breast cancer is one of the most prevalent diseases, inducing critical intimidation to human health. Lipid-based nanomaterials have been successfully demonstrated as drug carriers for breast cancer treatment. To date, the development of a better drug delivery system based on lipid nanomaterials is still urgent to make the treatment and diagnosis easily accessible to breast cancer patients. In a drug delivery system, lipid nanomaterials have revealed distinctive features, including high biocompatibility and efficient drug delivery. Specifically, a targeted drug delivery system based on lipid nanomaterials has inherited the advantage of optimum dosage and low side effects. In this review, insights on currently used potential lipid-based nanomaterials are collected and introduced. The review sheds light on conjugation, targeting, diagnosis, treatment, and clinical significance of lipid-based nanomaterials to treat breast cancer. Furthermore, a brighter side of lipid-based nanomaterials as future potential drug delivery systems for breast cancer therapy is discussed.
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Affiliation(s)
- Lekshmi Rethi
- International Ph.D. Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan
| | - Chinmaya Mutalik
- International Ph.D. Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan
| | - Dito Anurogo
- International Ph.D. Program for Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan or
- Faculty of Medicine and Health Sciences, Universitas Muhammadiyah Makassar, Makassar City 90221, South Sulawesi, Indonesia
| | - Long-Sheng Lu
- International Ph.D. Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan
- Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan
- Department of Radiation Oncology, Taipei Medical University Hospital, Taipei Medical University, Taipei 11031, Taiwan
| | - Hsiu-Yi Chu
- Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
| | - Sibidou Yougbaré
- Institut de Recherche en Sciences de la Santé/Direction Régionale du Centre Ouest (IRSS/DRCO), Nanoro BP 218, 11, Burkina Faso
| | - Tsung-Rong Kuo
- International Ph.D. Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan
- Graduate Institute of Nanomedicine and Medical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan
| | - Tsai-Mu Cheng
- Graduate Institute of Translational Medicine, College of Medicine and Technology, Taipei Medical University, Taipei 11031, Taiwan
- Taipei Heart Institute, Taipei Medical University, Taipei 11031, Taiwan
| | - Fu-Lun Chen
- Department of Internal Medicine, Division of Infectious Diseases, Taipei Municipal Wan Fang Hospital, Taipei Medical University, Taipei 11031, Taiwan
- Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
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16
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Ashrafizadeh M, Delfi M, Zarrabi A, Bigham A, Sharifi E, Rabiee N, Paiva-Santos AC, Kumar AP, Tan SC, Hushmandi K, Ren J, Zare EN, Makvandi P. Stimuli-responsive liposomal nanoformulations in cancer therapy: Pre-clinical & clinical approaches. J Control Release 2022; 351:50-80. [PMID: 35934254 DOI: 10.1016/j.jconrel.2022.08.001] [Citation(s) in RCA: 90] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 07/31/2022] [Accepted: 08/01/2022] [Indexed: 11/30/2022]
Abstract
The site-specific delivery of antitumor agents is of importance for providing effective cancer suppression. Poor bioavailability of anticancer compounds and the presence of biological barriers prevent their accumulation in tumor sites. These obstacles can be overcome using liposomal nanostructures. The challenges in cancer chemotherapy and stimuli-responsive nanocarriers are first described in the current review. Then, stimuli-responsive liposomes including pH-, redox-, enzyme-, light-, thermo- and magneto-sensitive nanoparticles are discussed and their potential for delivery of anticancer drugs is emphasized. The pH- or redox-sensitive liposomes are based on internal stimulus and release drug in response to a mildly acidic pH and GSH, respectively. The pH-sensitive liposomes can mediate endosomal escape via proton sponge. The multifunctional liposomes responsive to both redox and pH have more capacity in drug release at tumor site compared to pH- or redox-sensitive alone. The magnetic field and NIR irradiation can be exploited for external stimulation of liposomes. The light-responsive liposomes release drugs when they are exposed to irradiation; thermosensitive-liposomes release drugs at a temperature of >40 °C when there is hyperthermia; magneto-responsive liposomes release drugs in presence of magnetic field. These smart nanoliposomes also mediate co-delivery of drugs and genes in synergistic cancer therapy. Due to lack of long-term toxicity of liposomes, they can be utilized in near future for treatment of cancer patients.
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Affiliation(s)
- Milad Ashrafizadeh
- Faculty of Engineering and Natural Sciences, Sabanci University, Orta Mahalle, Üniversite Caddesi No. 27, Orhanlı, Tuzla, 34956 Istanbul, Turkey.
| | - Masoud Delfi
- Department of Chemical Sciences, University of Naples "Federico II", Complesso Universitario Monte S. Angelo, Via Cintia, Naples 80126, Italy
| | - Ali Zarrabi
- Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Istanbul 34396, Turkey
| | - Ashkan Bigham
- Institute of Polymers, Composites and Biomaterials-National Research Council (IPCB-CNR), Viale J.F. Kennedy 54-Mostra d'Oltremare pad. 20, 80125 Naples, Italy
| | - Esmaeel Sharifi
- Department of Tissue Engineering and Biomaterials, School of Advanced Medical Sciences and Technologies, Hamadan University of Medical Sciences, 6517838736 Hamadan, Iran
| | - Navid Rabiee
- Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk 37673, South Korea; School of Engineering, Macquarie University, Sydney, New South Wales 2109, Australia
| | - Ana Cláudia Paiva-Santos
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Azinhaga Sta. Comba, 3000-548 Coimbra, Portugal; LAQV, REQUIMTE, Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Azinhaga Sta. Comba, 3000-548 Coimbra, Portugal
| | - Alan Prem Kumar
- NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore; Cancer Science Institute of Singapore and Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore
| | - Shing Cheng Tan
- UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Kiavash Hushmandi
- Department of Food Hygiene and Quality Control, Division of Epidemiology and zoonosis, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Jun Ren
- Department of Cardiology, Zhongshan Hospital Fudan University, Shanghai 200032, China
| | | | - Pooyan Makvandi
- School of Chemistry, Damghan University, Damghan 36716-41167, Iran; Istituto Italiano di Tecnologia, Center for Materials Interfaces, viale Rinaldo Piaggio 34, 56025, Pontedera, Pisa, Italy.
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17
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Qu B, Han Y, Liang T, Zhang C, Hou G, Gao F. Evaluation of a novel EphA2 targeting peptide for triple negative breast cancer based on radionuclide molecular imaging. ARAB J CHEM 2022. [DOI: 10.1016/j.arabjc.2022.104211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
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18
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Eras A, Castillo D, Suárez M, Vispo NS, Albericio F, Rodriguez H. Chemical Conjugation in Drug Delivery Systems. Front Chem 2022; 10:889083. [PMID: 35720996 PMCID: PMC9204480 DOI: 10.3389/fchem.2022.889083] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 04/11/2022] [Indexed: 11/18/2022] Open
Abstract
Cancer is one of the diseases with the highest mortality rate. Treatments to mitigate cancer are usually so intense and invasive that they weaken the patient to cure as dangerous as the own disease. From some time ago until today, to reduce resistance generated by the constant administration of the drug and improve its pharmacokinetics, scientists have been developing drug delivery system (DDS) technology. DDS platforms aim to maximize the drugs’ effectiveness by directing them to reach the affected area by the disease and, therefore, reduce the potential side effects. Erythrocytes, antibodies, and nanoparticles have been used as carriers. Eleven antibody–drug conjugates (ADCs) involving covalent linkage has been commercialized as a promising cancer treatment in the last years. This review describes the general features and applications of DDS focused on the covalent conjugation system that binds the antibody carrier to the cytotoxic drug.
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Affiliation(s)
- Alexis Eras
- School of Chemical Sciences and Engineering, Yachay Tech University, Urcuquí, Ecuador
| | - Danna Castillo
- School of Chemical Sciences and Engineering, Yachay Tech University, Urcuquí, Ecuador
| | - Margarita Suárez
- Laboratorio de Síntesis Orgánica, Facultad de Química, Universidad de la Habana, La Habana, Cuba
| | - Nelson Santiago Vispo
- School of Biological Sciences and Engineering, Yachay Tech University, Urcuquí, Ecuador
- *Correspondence: Nelson Santiago Vispo, ; Fernando Albericio, ; Hortensia Rodriguez,
| | - Fernando Albericio
- Department of Surfactants and Nanobiotechnology, Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Barcelona, Spain
- CIBER-BBN, Networking Centre of Bioengineering, Biomaterials, and Nanomedicine and Department of Organic Chemistry, University of Barcelona, Barcelona, Spain
- School of Chemistry and Physics, University of KwaZulu-Natal, Durban, South Africa
- *Correspondence: Nelson Santiago Vispo, ; Fernando Albericio, ; Hortensia Rodriguez,
| | - Hortensia Rodriguez
- School of Chemical Sciences and Engineering, Yachay Tech University, Urcuquí, Ecuador
- *Correspondence: Nelson Santiago Vispo, ; Fernando Albericio, ; Hortensia Rodriguez,
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19
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Chaudhuri A, Kumar DN, Dehari D, Singh S, Kumar P, Bolla PK, Kumar D, Agrawal AK. Emergence of Nanotechnology as a Powerful Cavalry against Triple-Negative Breast Cancer (TNBC). Pharmaceuticals (Basel) 2022; 15:542. [PMID: 35631368 PMCID: PMC9143332 DOI: 10.3390/ph15050542] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 04/26/2022] [Accepted: 04/26/2022] [Indexed: 12/11/2022] Open
Abstract
Triple-negative breast cancer (TNBC) is considered one of the un-manageable types of breast cancer, involving devoid of estrogen, progesterone, and human epidermal growth factor receptor 2 (HER 2) receptors. Due to their ability of recurrence and metastasis, the management of TNBC remains a mainstay challenge, despite the advancements in cancer therapies. Conventional chemotherapy remains the only treatment regimen against TNBC and suffers several limitations such as low bioavailability, systemic toxicity, less targetability, and multi-drug resistance. Although various targeted therapies have been introduced to manage the hardship of TNBC, they still experience certain limitations associated with the survival benefits. The current research thus aimed at developing and improving the strategies for effective therapy against TNBC. Such strategies involved the emergence of nanoparticles. Nanoparticles are designated as nanocavalries, loaded with various agents (drugs, genes, etc.) to battle the progression and metastasis of TNBC along with overcoming the limitations experienced by conventional chemotherapy and targeted therapy. This article documents the treatment regimens of TNBC along with their efficacy towards different subtypes of TNBC, and the various nanotechnologies employed to increase the therapeutic outcome of FDA-approved drug regimens.
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Affiliation(s)
- Aiswarya Chaudhuri
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi 221005, India; (A.C.); (D.N.K.); (D.D.); (S.S.); (D.K.)
| | - Dulla Naveen Kumar
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi 221005, India; (A.C.); (D.N.K.); (D.D.); (S.S.); (D.K.)
| | - Deepa Dehari
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi 221005, India; (A.C.); (D.N.K.); (D.D.); (S.S.); (D.K.)
| | - Sanjay Singh
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi 221005, India; (A.C.); (D.N.K.); (D.D.); (S.S.); (D.K.)
- Babasaheb Bhimrao Ambedkar University, Lucknow 226025, India
| | - Pradeep Kumar
- Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa;
| | - Pradeep Kumar Bolla
- Department of Biomedical Engineering, College of Engineering, The University of Texas at El Paso, 500 W. University Ave, El Paso, TX 79968, USA;
| | - Dinesh Kumar
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi 221005, India; (A.C.); (D.N.K.); (D.D.); (S.S.); (D.K.)
| | - Ashish Kumar Agrawal
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi 221005, India; (A.C.); (D.N.K.); (D.D.); (S.S.); (D.K.)
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Banthia P, Gambhir L, Sharma A, Daga D, Kapoor N, Chaudhary R, Sharma G. Nano to rescue: repository of nanocarriers for targeted drug delivery to curb breast cancer. 3 Biotech 2022; 12:70. [PMID: 35223356 PMCID: PMC8841383 DOI: 10.1007/s13205-022-03121-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 01/16/2022] [Indexed: 12/17/2022] Open
Abstract
Breast cancer is a heterogeneous disease with different intrinsic subtypes. The conventional treatment of surgical resection, chemotherapy, immunotherapy and radiotherapy has not shown significant improvement in the survival rate of breast cancer patients. The therapeutics used cause bystander toxicities deteriorating healthy tissues. The breakthroughs of nanotechnology have been a promising feat in selective targeting of tumor site thus increasing the therapeutic gain. By the application of nanoenabled carriers, nanomedicines ensure targeted delivery, stability, enhanced cellular uptake, biocompatibility and higher apoptotic efficacy. The present review focuses on breakthrough of nanoscale intervention in targeted drug delivery as novel class of therapeutics. Nanoenabled carriers like polymeric and metallic nanoparticles, dendrimers, quantum dots, liposomes, solid lipid nanoparticles, carbon nanotubes, drug-antibody conjugates and exosomes revolutionized the targeted therapeutic delivery approach. These nanoassemblies have shown additional effect of improving the solubility of drugs such as paclitaxel, reducing the dose and toxicity. The present review provides an insight on the different drug conjugates employed/investigated to curb breast cancer using nanocarrier mediated targeted drug delivery. However, identification of appropriate biomarkers to target, clearer insight of the biological processes, batch uniformity, reproducibility, nanomaterial toxicity and stabilities are the hurdles faced by nanodrugs. The potential of nano-therapeutics delivery necessitates the agglomerated efforts of research community to bridge the route of nanodrugs for scale-up, commercialization and clinical applications.
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Affiliation(s)
- Poonam Banthia
- School of Applied Sciences, Suresh Gyan Vihar University, Jaipur, Rajasthan India
| | - Lokesh Gambhir
- School of Applied Sciences, Suresh Gyan Vihar University, Jaipur, Rajasthan India
| | - Asha Sharma
- Department of Zoology, Swargiya P. N. K. S. Govt. PG College, Dausa, Rajasthan India
| | - Dhiraj Daga
- Department of Radiation Oncology, JLN Medical College, Ajmer, Rajasthan India
| | - Neha Kapoor
- School of Applied Sciences, Suresh Gyan Vihar University, Jaipur, Rajasthan India
| | - Rishabh Chaudhary
- Department of Emergency Medicine, Institute of Bioelectronic Medicine, Feinstein Institute of Medical Research, Northwell Health, New Hyde Park, NY USA
| | - Gaurav Sharma
- School of Applied Sciences, Suresh Gyan Vihar University, Jaipur, Rajasthan India
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21
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Tripathi AK, Ray AK, Mishra SK. Molecular and pharmacological aspects of piperine as a potential molecule for disease prevention and management: evidence from clinical trials. BENI-SUEF UNIVERSITY JOURNAL OF BASIC AND APPLIED SCIENCES 2022; 11:16. [PMID: 35127957 PMCID: PMC8796742 DOI: 10.1186/s43088-022-00196-1] [Citation(s) in RCA: 67] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 01/11/2022] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Piperine is a type of amide alkaloid that exhibits pleiotropic properties like antioxidant, anticancer, anti-inflammatory, antihypertensive, hepatoprotective, neuroprotective and enhancing bioavailability and fertility-related activities. Piperine has the ability to alter gastrointestinal disorders, drug-metabolizing enzymes, and bioavailability of several drugs. The present review explores the available clinical and preclinical data, nanoformulations, extraction process, structure-activity relationships, molecular docking, bioavailability enhancement of phytochemicals and drugs, and brain penetration properties of piperine in the prevention, management, and treatment of various diseases and disorders. MAIN BODY Piperine provides therapeutic benefits in patients suffering from diabetes, obesity, arthritis, oral cancer, breast cancer, multiple myeloma, metabolic syndrome, hypertension, Parkinson's disease, Alzheimer's disease, cerebral stroke, cardiovascular diseases, kidney diseases, inflammatory diseases, and rhinopharyngitis. The molecular basis for the pleiotropic activities of piperine is based on its ability to regulate multiple signaling molecules such as cell cycle proteins, anti-apoptotic proteins, P-glycoprotein, cytochrome P450 3A4, multidrug resistance protein 1, breast cancer resistance protein, transient receptor potential vanilloid 1 proinflammatory cytokine, nuclear factor-κB, c-Fos, cAMP response element-binding protein, activation transcription factor-2, peroxisome proliferator-activated receptor-gamma, Human G-quadruplex DNA, Cyclooxygenase-2, Nitric oxide synthases-2, MicroRNA, and coronaviruses. Piperine also regulates multiple signaling pathways such as Akt/mTOR/MMP-9, 5'-AMP-activated protein kinase-activated NLR family pyrin domain containing-3 inflammasome, voltage-gated K+ current, PKCα/ERK1/2, NF-κB/AP-1/MMP-9, Wnt/β-catenin, JNK/P38 MAPK, and gut microbiota. SHORT CONCLUSION Based on the current evidence, piperine can be the potential molecule for treatment of disease, and its significance of this molecule in the clinic is discussed. GRAPHICAL ABSTRACT
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Affiliation(s)
- Amit Kumar Tripathi
- Molecular Biology Unit, Institute of Medical Science, Banaras Hindu University, Varanasi, 221005 India
- Clinical Research Division, School of Basic and Applied Science, Galgotias University, Gautam Buddha Nagar, UP India
| | - Anup Kumar Ray
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University, Varanasi, 221005 India
- Department of Pharmacognosy, I.T.S College of Pharmacy, Ghaziabad, UP 201206 India
| | - Sunil Kumar Mishra
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University, Varanasi, 221005 India
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Khodaverdi H, Zeini MS, Moghaddam MM, Vazifedust S, Akbariqomi M, Tebyanian H. Lipid-Based Nanoparticles for Targeted Delivery of the Anti-Cancer Drugs: A Review. Curr Drug Deliv 2022; 19:1012-1033. [DOI: 10.2174/1567201819666220117102658] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 11/01/2021] [Accepted: 12/01/2021] [Indexed: 11/22/2022]
Abstract
Abstract:
Cancer is one of the main reasons for mortality worldwide. Chemotherapeutic agents have been effectively designed to increase certain patients' survival rates, but ordinarily designed chemotherapeutic agents necessarily deliver toxic chemotherapeutic drugs to healthy tissues, resulting in serious side effects. Cancer cells can often acquire drug resistance after repeated dosing of current chemotherapeutic agents, restricting their efficacy. Given such obstacles, investigators have attempted to distribute chemotherapeutic agents using targeted drug delivery systems (DDSs), especially nanotechnology-based DDSs. Lipid-Based Nanoparticles (LBNPs) are a large and complex class of substances that have been utilized to manage a variety of diseases, mostly cancer. Liposomes seem to be the most frequently employed LBNPs, owing to their high biocompatibility, bioactivity, stability, and flexibility; howbeit Solid Lipid Nanoparticles (SLNs) and Non-structured Lipid Carriers (NLCs) have lately received a lot of interest. Besides that, there are several reports that concentrate on novel therapies via LBNPs to manage various forms of cancer. In the present research, the latest improvements in the application of LBNPs have been shown to deliver different therapeutic agents to cancerous cells and have been demonstrated LBNPs also can be a quite successful candidate in cancer therapy for subsequent use.
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Affiliation(s)
- Hamed Khodaverdi
- National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran
| | - Maryam Shokrian Zeini
- Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | | | | | - Mostafa Akbariqomi
- Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Hamid Tebyanian
- School of Dentistry, Baqiyatallah University of Medical Sciences, Tehran, Iran
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Mehata AK, Muthu MS. Development of Supramolecules in the Field of Nanomedicines. PHARMACEUTICAL APPLICATIONS OF SUPRAMOLECULES 2022:211-239. [DOI: 10.1007/978-3-031-21900-9_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
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Shang L, Zhou X, Zhang J, Shi Y, Zhong L. Metal Nanoparticles for Photodynamic Therapy: A Potential Treatment for Breast Cancer. Molecules 2021; 26:molecules26216532. [PMID: 34770941 PMCID: PMC8588551 DOI: 10.3390/molecules26216532] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 10/13/2021] [Accepted: 10/26/2021] [Indexed: 12/12/2022] Open
Abstract
Breast cancer (BC) is the most common malignant tumor in women worldwide, which seriously threatens women’s physical and mental health. In recent years, photodynamic therapy (PDT) has shown significant advantages in cancer treatment. PDT involves activating photosensitizers with appropriate wavelengths of light, producing transient levels of reactive oxygen species (ROS). Compared with free photosensitizers, the use of nanoparticles in PDT shows great advantages in terms of solubility, early degradation, and biodistribution, as well as more effective intercellular penetration and targeted cancer cell uptake. Under the current circumstances, researchers have made promising efforts to develop nanocarrier photosensitizers. Reasonably designed photosensitizer (PS) nanoparticles can be achieved through non-covalent (self-aggregation, interfacial deposition, interfacial polymerization or core-shell embedding and physical adsorption) or covalent (chemical immobilization or coupling) processes and accumulate in certain tumors through passive and/or active targeting. These PS loading methods provide chemical and physical stability to the PS payload. Among nanoparticles, metal nanoparticles have the advantages of high stability, adjustable size, optical properties, and easy surface functionalization, making them more biocompatible in biological applications. In this review, we summarize the current development and application status of photodynamic therapy for breast cancer, especially the latest developments in the application of metal nanocarriers in breast cancer PDT, and highlight some of the recent synergistic therapies, hopefully providing an accessible overview of the current knowledge that may act as a basis for new ideas or systematic evaluations of already promising results.
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Affiliation(s)
- Liang Shang
- Department of Breast Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China; (L.S.); (J.Z.); or (Y.S.)
| | - Xinglu Zhou
- Department of PET/CT Center, Harbin Medical University Cancer Hospital, Harbin 150081, China;
| | - Jiarui Zhang
- Department of Breast Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China; (L.S.); (J.Z.); or (Y.S.)
| | - Yujie Shi
- Department of Breast Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China; (L.S.); (J.Z.); or (Y.S.)
| | - Lei Zhong
- Department of Breast Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China; (L.S.); (J.Z.); or (Y.S.)
- Department of Breast Surgery, Sixth Affiliated Hospital of Harbin Medical University, Harbin 150086, China
- Correspondence:
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Quijia CR, Chorilli M. Piperine for treating breast cancer: A review of molecular mechanisms, combination with anticancer drugs, and nanosystems. Phytother Res 2021; 36:147-163. [PMID: 34559416 DOI: 10.1002/ptr.7291] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 07/30/2021] [Accepted: 08/25/2021] [Indexed: 12/12/2022]
Abstract
Piperine (PIP) is an alkaloid found primarily in Piper longum, and this natural compound has been shown to exert effects on proliferation and survival against various types of cancer. In particular, PIP has potent inhibitory effects on breast cancer (BC), the most prevalent type of cancer in women worldwide. PIP targets numerous signaling pathways associated with the therapy of BC cells through the following mechanisms: (a) induction of arrest of the cell cycle and apoptosis; (b) alteration of the signaling protein expression; (c) reduction in transcription factors; and (d) inhibition of tumor growth. BC cells have the ability to resist conventional drugs, so one of the strategies is the combination of PIP with other phytochemicals such as paclitaxel, thymoquinone, hesperidin, bee venom, tamoxifen, mitoxantrone, piperlongumin, and curcumin. Nanotechnology-based drug encapsulation systems are currently used to enhance the release of PIP. This includes polymer nanoparticles, carbon nanotubes, and liposomes. In the present review, the chemistry and bioavailability of PIP, its molecular targets in BC, and nanotechnological strategies are discussed. Future research directions are also discussed to further understand this promising natural product.
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Affiliation(s)
| | - Marlus Chorilli
- School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, Brazil
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Triple negative breast cancer and non-small cell lung cancer: Clinical challenges and nano-formulation approaches. J Control Release 2021; 337:27-58. [PMID: 34273417 DOI: 10.1016/j.jconrel.2021.07.014] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 07/08/2021] [Accepted: 07/10/2021] [Indexed: 02/06/2023]
Abstract
Triple negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC) are amongst the most aggressive forms of solid tumors. TNBC is highlighted by absence of genetic components of progesterone receptor, HER2/neu and estrogen receptor in breast cancer. NSCLC is characterized by integration of malignant carcinoma into respiratory system. Both cancers are associated with poor median and overall survival rates with low progression free survival with high incidences of relapse. These cancers are characterized by tumor heterogeneity, genetic mutations, generation of cancer-stem cells, immune-resistance and chemoresistance. Further, these neoplasms have been reported for tumor cross-talk into second primary cancers for each other. Current chemotherapeutic regimens include usage of multiple agents in tandem to affect tumor cells through multiple mechanisms with various such combinations being clinically tested. However, lack of controlled delivery and effective temporospatial presence of chemotherapeutics has resulted in suboptimal therapeutic response. Consequently, passive targeted albumin bound paclitaxel and PEGylated liposomal doxorubicin have been clinically used and tested with newer drugs for improved therapeutic efficacy in these cancers. Active targeting of nanocarriers against surface overexpressed proteins in both neoplasms have been explored. However, use of single agent nanoparticulate formulations against both cancers have failed to elicit desired outcomes. This review aims to identify clinical unmet need in these cancers while establishing a correlation with tested nano-formulation approaches and issues with preclinical to clinical translation. Lipid and polymer-based drug-drug and drug-gene combinatorial nanocarriers delivering multiple chemotherapeutics simultaneously to desired site of action have been detailed. Finally, emerging opportunities such as pharmacological targets (immune check point and epigentic modulators) as well as gene-based modulation (siRNA/CRISPR/Cas9) and the nano-formulation challenges for effective treatment of both cancers have been explored.
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Imam SS, Alshehri S, Altamimi MA, Hussain A, Qamar W, Gilani SJ, Zafar A, Alruwaili NK, Alanazi S, Almutairy BK. Formulation of Piperine-Chitosan-Coated Liposomes: Characterization and In Vitro Cytotoxic Evaluation. Molecules 2021; 26:molecules26113281. [PMID: 34072306 PMCID: PMC8198173 DOI: 10.3390/molecules26113281] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 05/24/2021] [Accepted: 05/27/2021] [Indexed: 01/23/2023] Open
Abstract
The present research work is designed to prepare and evaluate piperine liposomes and piperine–chitosan-coated liposomes for oral delivery. Piperine (PPN) is a water-insoluble bioactive compound used for different diseases. The prepared formulations were evaluated for physicochemical study, mucoadhesive study, permeation study and in vitro cytotoxic study using the MCF7 breast cancer cell line. Piperine-loaded liposomes (PLF) were prepared by the thin-film evaporation method. The selected liposomes were coated with chitosan (PLFC) by electrostatic deposition to enhance the mucoadhesive property and in vitro therapeutic efficacy. Based on the findings of the study, the prepared PPN liposomes (PLF3) and chitosan coated PPN liposomes (PLF3C1) showed a nanometric size range of 165.7 ± 7.4 to 243.4 ± 7.5, a narrow polydispersity index (>0.3) and zeta potential (−7.1 to 29.8 mV). The average encapsulation efficiency was found to be between 60 and 80% for all prepared formulations. The drug release and permeation study profile showed biphasic release behavior and enhanced PPN permeation. The in vitro antioxidant study results showed a comparable antioxidant activity with pure PPN. The anticancer study depicted that the cell viability assay of tested PLF3C2 has significantly (p < 0.001)) reduced the IC50 when compared with pure PPN. The study revealed that oral chitosan-coated liposomes are a promising delivery system for the PPN and can increase the therapeutic efficacy against the breast cancer cell line.
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Affiliation(s)
- Syed Sarim Imam
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; (S.S.I.); (M.A.A.); (A.H.); (S.A.)
| | - Sultan Alshehri
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; (S.S.I.); (M.A.A.); (A.H.); (S.A.)
- Correspondence:
| | - Mohammad A. Altamimi
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; (S.S.I.); (M.A.A.); (A.H.); (S.A.)
| | - Afzal Hussain
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; (S.S.I.); (M.A.A.); (A.H.); (S.A.)
| | - Wajhul Qamar
- Central Laboratory, Research Center, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia;
| | - Sadaf Jamal Gilani
- Department of Basic Health Sciences, Preparatory Year, Princess Nourahbint Adbulrahman University, Riyadh 11671, Saudi Arabia;
| | - Ameeduzzafar Zafar
- Department of Pharmaceutics, College of Pharmacy, Jouf University, Aljouf Region, Sakaka 72341, Saudi Arabia; (A.Z.); (N.K.A.)
| | - Nabil K. Alruwaili
- Department of Pharmaceutics, College of Pharmacy, Jouf University, Aljouf Region, Sakaka 72341, Saudi Arabia; (A.Z.); (N.K.A.)
| | - Saleh Alanazi
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; (S.S.I.); (M.A.A.); (A.H.); (S.A.)
| | - Bjad K. Almutairy
- Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj 11942, Saudi Arabia;
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Novel redox-sensitive thiolated TPGS based nanoparticles for EGFR targeted lung cancer therapy. Int J Pharm 2021; 602:120652. [PMID: 33915187 DOI: 10.1016/j.ijpharm.2021.120652] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 04/06/2021] [Accepted: 04/23/2021] [Indexed: 12/22/2022]
Abstract
Novel glutathione (GSH) redox-sensitive thiolated vitaminE-PEG1000-succinate (TPGH-SH) was synthesized by conjugating TPGS with 4-amino thiophenol (4-ATP) and confirmed by FTIR and NMR studies. Following, docetaxel (DTX) loaded, cetuximab (CTB) conjugated redox sensitive TPGS-SH nanoparticles (TPGS-SH NP) were prepared by dialysis method and screened for size, charge, DTX entrapment, which revealed that size, surface charge and percent entrapment are in the range of 183-227 nm, +18 to +26 mV and 68-71%. SEM, TEM, AFM have reflected the spherical and uniform size of NP with a smooth surface. In-vitro release studies were performed in media containing different concentrations of GSH to study their effect on drug release and drug release of up to 94.5%, at pH 5.5, GSH 20 mM, is observed within 24 h. The pH/redox sensitivity studies revealed the better stability of NP at higher pH and lower GSH concentrations. In-vitro cytotoxicity, cellular uptake, migration and apoptotic assays, performed on A549 cells, have proved that targeted formulation produced higher cytotoxicity (significantly less IC50 value) and uptake and also prevented cell migration. Pharmacokinetic and histopathological screening were performed on CF rats, which demonstrated promising results. The in-vivo efficacy studies on benzo(a)pyrene induced mice lung cancer model showed that targeted TPGS-SH NP has significantly reduced the cell number than the model control.
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Kundu M, Majumder R, Das CK, Mandal M. Natural products based nanoformulations for cancer treatment: Current evolution in Indian research. Biomed Mater 2021; 16. [PMID: 33621207 DOI: 10.1088/1748-605x/abe8f2] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Accepted: 02/23/2021] [Indexed: 12/17/2022]
Abstract
The use of medicinal plants is as ancient as human civilization. The development of phytochemistry and pharmacology facilitates the identification of natural bioactive compounds and their mechanisms of action, including against cancer. The efficacy and the safety of a bioactive compound depend on its optimal delivery to the target site. Most natural bioactive compounds (phenols, flavonoids, tannins, etc.) are unable to reach their target sites due to their low water solubility, less cellular absorption, and high molecular weight, leading to their failure into clinical translation. Therefore, many scientific studies are going on to overcome the drawbacks of natural products for clinical applications. Several studies in India, as well as worldwide, have proposed the development of natural products-based nanoformulations to increase their efficacy and safety profile for cancer therapy by improving the delivery of natural bioactive compounds to their target site. Therefore, we are trying to discuss the development of natural products-based nanoformulations in India to improve the efficacy and safety of natural bioactive compounds against cancer.
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Affiliation(s)
- Moumita Kundu
- Indian Institute of Technology Kharagpur, Cancer biology lab, Kharagpur, West Bengal, 721302, INDIA
| | - Ranabir Majumder
- Indian Institute of Technology Kharagpur, Cancer biology lab, Kharagpur, West Bengal, 721302, INDIA
| | - Chandan Kanta Das
- Indian Institute of Technology Kharagpur, Cancer biology lab, Kharagpur, West Bengal, 721302, INDIA
| | - Mahitosh Mandal
- SMST, Indian Institute of Technology Kharagpur, Cancer biology lab, Kharagpur, 721302, INDIA
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Malavia N, Kuche K, Ghadi R, Jain S. A bird's eye view of the advanced approaches and strategies for overshadowing triple negative breast cancer. J Control Release 2020; 330:72-100. [PMID: 33321156 DOI: 10.1016/j.jconrel.2020.12.012] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Revised: 12/07/2020] [Accepted: 12/09/2020] [Indexed: 12/12/2022]
Abstract
Triple negative breast cancer (TNBC) is one of the most aggressive form of breast cancer. It is characterized by the absence of estrogen, progesterone and human epidermal growth factor receptors. The main issue with TNBC is that it exhibits poor prognosis, high risk of relapse, short progression-free survival and low overall survival in patients. This is because the conventional therapy used for managing TNBC has issues pertaining to poor bioavailability, lower cellular uptake, increased off-target effects and development of resistance. To overcome such pitfalls, several other approaches are explored. In this context, the present manuscript showcases three of the most widely used approaches which are (i) nanotechnology-based approach; (ii) gene therapy approach and (iii) Phytochemical-based approach. The ultimate focus is to present and explain the insightful reports based on these approaches. Further, the review also expounds on the identified molecular targets and novel targeting ligands which are explored for managing TNBC effectively. Thus, in a nutshell, the review tries to highlight these existing treatment approaches which might inspire for future development of novel therapies with a potential of overshadowing TNBC.
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Affiliation(s)
- Nilesh Malavia
- Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, S.A.S Nagar, Mohali, Punjab, India
| | - Kaushik Kuche
- Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, S.A.S Nagar, Mohali, Punjab, India
| | - Rohan Ghadi
- Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, S.A.S Nagar, Mohali, Punjab, India
| | - Sanyog Jain
- Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, S.A.S Nagar, Mohali, Punjab, India.
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Scaria B, Sood S, Raad C, Khanafer J, Jayachandiran R, Pupulin A, Grewal S, Okoko M, Arora M, Miles L, Pandey S. Natural Health Products (NHP's) and Natural Compounds as Therapeutic Agents for the Treatment of Cancer; Mechanisms of Anti-Cancer Activity of Natural Compounds and Overall Trends. Int J Mol Sci 2020; 21:E8480. [PMID: 33187200 PMCID: PMC7697102 DOI: 10.3390/ijms21228480] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 11/08/2020] [Accepted: 11/09/2020] [Indexed: 12/12/2022] Open
Abstract
Most cancer therapeutics, such as tubulin-targeting chemotherapy drugs, cause cytotoxic, non-selective effects. These harmful side-effects drastically reduce the cancer patient's quality of life. Recently, researchers have focused their efforts on studying natural health products (NHP's) which have demonstrated the ability to selectively target cancer cells in cellular and animal models. However, the major hurdle of clinical validation remains. NHP's warrant further clinical investigation as a therapeutic option since they exhibit low toxicity, while retaining a selective effect. Additionally, they can sensitize cancerous cells to chemotherapy, which enhances the efficacy of chemotherapeutic drugs, indicating that they can be utilized as supplemental therapy. An additional area for further research is the investigation of drug-drug interactions between NHP's and chemotherapeutics. The objectives of this review are to report the most recent results from the field of anticancer NHP research, and to highlight the most recent advancements in possible supplemental therapeutic options.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Siyaram Pandey
- Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON N9B 3P4, Canada; (B.S.); (S.S.); (C.R.); (J.K.); (R.J.); (A.P.); (S.G.); (M.O.); (M.A.); (L.M.)
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Viswanadh MK, Vikas, Jha A, Reddy Adena SK, Mehata AK, Priya V, Neogi K, Poddar S, Mahto SK, Muthu MS. Formulation and in vivo efficacy study of cetuximab decorated targeted bioadhesive nanomedicine for non-small-cell lung cancer therapy. Nanomedicine (Lond) 2020; 15:2345-2367. [DOI: 10.2217/nnm-2020-0167] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Aim: To design, optimize and evaluate docetaxel-loaded chitosan nanoparticles with (targeted) and without (nontargeted) cetuximab conjugation for the treatment of non-small-cell lung cancer (NSCLC). Materials & methods: Risk-assessment, optimization, in vitro characterizations, stability assessments, release studies, cell-culture studies were performed along with histopathology, pharmacokinetic and anticancer efficacy studies. Results: The nanoparticles of desired particle size (152.59 ± 3.90 nm to 180.63 ± 5.21 nm) which could sustain drug release for up to 70 h, were obtained. The cell-culture studies demonstrated the superiority of the formulations over Docel™. The pharmacokinetic evaluation showed the excellent systemic bioavailability of prepared NPs. The histopathology screening revealed lesser toxicity of both the nontargeted and targeted formulations. The targeted nanoformulation significantly reduced tumor growth than the nontargeted formulation and Docel. Conclusion: These results demonstrate the therapeutic potential of the prepared nanoformulation. After proper clinical validation, it could be a promising approach for the treatment of NSCLC.
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Affiliation(s)
- Matte Kasi Viswanadh
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi – 221005, India
| | - Vikas
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi – 221005, India
| | - Abhishek Jha
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi – 221005, India
| | - Sandeep Kumar Reddy Adena
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi – 221005, India
| | - Abhishesh Kumar Mehata
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi – 221005, India
| | - Vishnu Priya
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi – 221005, India
| | - Kaushik Neogi
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi – 221005, India
| | - Suruchi Poddar
- School of Biomedical Engineering, Indian Institute of Technology (BHU), Varanasi – 221005, India
| | - Sanjeev Kumar Mahto
- School of Biomedical Engineering, Indian Institute of Technology (BHU), Varanasi – 221005, India
| | - Madaswamy S Muthu
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi – 221005, India
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