CD44-Receptors-Mediated Multiprong Targeting Strategy Against Breast Cancer and Tumor-Associated Macrophages: Design, Optimization, Characterization, and Cytologic Evaluation
Zahid Hussain,1,2 Lama Abdulrahim Abdul Moti,1 Jayalakshmi Jagal,2 Hnin Ei Thu,3 Shahzeb Khan,4 Mohsin Kazi5 1Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates; 2Research Institute for Medical and Health Scienc...
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Dove Medical Press
2025-01-01
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| author | Hussain Z Abdulrahim Abdul Moti L Jagal J Thu HE Khan S Kazi M |
| author_facet | Hussain Z Abdulrahim Abdul Moti L Jagal J Thu HE Khan S Kazi M |
| author_sort | Hussain Z |
| collection | DOAJ |
| description | Zahid Hussain,1,2 Lama Abdulrahim Abdul Moti,1 Jayalakshmi Jagal,2 Hnin Ei Thu,3 Shahzeb Khan,4 Mohsin Kazi5 1Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates; 2Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates; 3Department of Pharmacology, Faculty of Dentistry, Universiti Teknologi MARA, Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia; 4Center for Pharmaceutical Engineering Science, Faculty of Life Sciences, School of Pharmacy and Medical Sciences, University of Bradford, West Yorkshire Bradford, BD7 1DP, UK; 5Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, 11451 Saudi ArabiaCorrespondence: Zahid Hussain, Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates, Email zhussain@sharjah.ac.aeIntroduction: Owing to its high prevalence, colossal potential of chemoresistance, metastasis, and relapse, breast cancer (BC) is the second leading cause of cancer-related fatalities in women. Several treatments (eg, chemotherapy, surgery, radiations, hormonal therapy, etc.) are conventionally prescribed for the treatment of BC; however, these are associated with serious systemic aftermaths. In this research, we aimed to design a multiprong targeting strategy for concurrent action against different phenotypes of BC (MCF-7 and SK-BR-3) and tumor-associated macrophages (TAMs) for relapse-free treatment of BC.Methods: Paclitaxel (PTX) and tamoxifen (TMX) co-loaded chitosan (CS) nanoparticles (NPs) were prepared using the ionic-gelation method and optimized using the Design Expert® software by controlling different material attributes. For selective targeting through CD44-receptors that are heavily expressed on the BC cells and TAMs, the fabricated NPs (PTX-TMX-CS-NPs) were functionalized with hyaluronic acid (HA) as a targeting ligand.Results: The optimized HA-PTX-TMX-CS-NPs exhibited desired physicochemical properties (PS ~230 nm, PDI 0.30, zeta potential ~21.5 mV), smooth spherical morphology, high encapsulation efficiency (PTX ~72% and TMX ~97%), good colloidal stability, and biphasic release kinetics. Moreover, the lowest cell viability depicted in MCF-7 (~25%), SK-BR-3 (~20%), and RAW 264.7 cells (~20%), induction of apoptosis, cell cycle arrest, enhanced cell internalization, and alleviation of MCF-7 and SK-BR-3 migration proved the superior anticancer potential of HA-PTX-TMX-CS-NPs compared to unfunctionalized NPs and other control medicines.Conclusion: HA-functionalization of NPs is a promising multiprong strategy for CD44-receptors-mediated targeting of BC cells and TAMs to mitigate the progression, metastasis, and relapse in the BC. Keywords: paclitaxel, tamoxifen, hyaluronic acid, polymeric nanoparticles, CD44-receptors, breast cancer, cell uptake, anticancer efficacy |
| format | Article |
| id | doaj-art-0032fdb669b04ca7b8c1a54c8a1ae3c2 |
| institution | Kabale University |
| issn | 1178-2013 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Dove Medical Press |
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| series | International Journal of Nanomedicine |
| spelling | doaj-art-0032fdb669b04ca7b8c1a54c8a1ae3c22025-01-27T18:05:34ZengDove Medical PressInternational Journal of Nanomedicine1178-20132025-01-01Volume 20991102099572CD44-Receptors-Mediated Multiprong Targeting Strategy Against Breast Cancer and Tumor-Associated Macrophages: Design, Optimization, Characterization, and Cytologic EvaluationHussain ZAbdulrahim Abdul Moti LJagal JThu HEKhan SKazi MZahid Hussain,1,2 Lama Abdulrahim Abdul Moti,1 Jayalakshmi Jagal,2 Hnin Ei Thu,3 Shahzeb Khan,4 Mohsin Kazi5 1Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates; 2Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates; 3Department of Pharmacology, Faculty of Dentistry, Universiti Teknologi MARA, Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia; 4Center for Pharmaceutical Engineering Science, Faculty of Life Sciences, School of Pharmacy and Medical Sciences, University of Bradford, West Yorkshire Bradford, BD7 1DP, UK; 5Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, 11451 Saudi ArabiaCorrespondence: Zahid Hussain, Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates, Email zhussain@sharjah.ac.aeIntroduction: Owing to its high prevalence, colossal potential of chemoresistance, metastasis, and relapse, breast cancer (BC) is the second leading cause of cancer-related fatalities in women. Several treatments (eg, chemotherapy, surgery, radiations, hormonal therapy, etc.) are conventionally prescribed for the treatment of BC; however, these are associated with serious systemic aftermaths. In this research, we aimed to design a multiprong targeting strategy for concurrent action against different phenotypes of BC (MCF-7 and SK-BR-3) and tumor-associated macrophages (TAMs) for relapse-free treatment of BC.Methods: Paclitaxel (PTX) and tamoxifen (TMX) co-loaded chitosan (CS) nanoparticles (NPs) were prepared using the ionic-gelation method and optimized using the Design Expert® software by controlling different material attributes. For selective targeting through CD44-receptors that are heavily expressed on the BC cells and TAMs, the fabricated NPs (PTX-TMX-CS-NPs) were functionalized with hyaluronic acid (HA) as a targeting ligand.Results: The optimized HA-PTX-TMX-CS-NPs exhibited desired physicochemical properties (PS ~230 nm, PDI 0.30, zeta potential ~21.5 mV), smooth spherical morphology, high encapsulation efficiency (PTX ~72% and TMX ~97%), good colloidal stability, and biphasic release kinetics. Moreover, the lowest cell viability depicted in MCF-7 (~25%), SK-BR-3 (~20%), and RAW 264.7 cells (~20%), induction of apoptosis, cell cycle arrest, enhanced cell internalization, and alleviation of MCF-7 and SK-BR-3 migration proved the superior anticancer potential of HA-PTX-TMX-CS-NPs compared to unfunctionalized NPs and other control medicines.Conclusion: HA-functionalization of NPs is a promising multiprong strategy for CD44-receptors-mediated targeting of BC cells and TAMs to mitigate the progression, metastasis, and relapse in the BC. Keywords: paclitaxel, tamoxifen, hyaluronic acid, polymeric nanoparticles, CD44-receptors, breast cancer, cell uptake, anticancer efficacyhttps://www.dovepress.com/cd44-receptors-mediated-multiprong-targeting-strategy-against-breast-c-peer-reviewed-fulltext-article-IJNpaclitaxeltamoxifenhyaluronic acidpolymeric nanoparticlescd44-receptorsbreast cancercell uptakeanticancer efficacy |
| spellingShingle | Hussain Z Abdulrahim Abdul Moti L Jagal J Thu HE Khan S Kazi M CD44-Receptors-Mediated Multiprong Targeting Strategy Against Breast Cancer and Tumor-Associated Macrophages: Design, Optimization, Characterization, and Cytologic Evaluation International Journal of Nanomedicine paclitaxel tamoxifen hyaluronic acid polymeric nanoparticles cd44-receptors breast cancer cell uptake anticancer efficacy |
| title | CD44-Receptors-Mediated Multiprong Targeting Strategy Against Breast Cancer and Tumor-Associated Macrophages: Design, Optimization, Characterization, and Cytologic Evaluation |
| title_full | CD44-Receptors-Mediated Multiprong Targeting Strategy Against Breast Cancer and Tumor-Associated Macrophages: Design, Optimization, Characterization, and Cytologic Evaluation |
| title_fullStr | CD44-Receptors-Mediated Multiprong Targeting Strategy Against Breast Cancer and Tumor-Associated Macrophages: Design, Optimization, Characterization, and Cytologic Evaluation |
| title_full_unstemmed | CD44-Receptors-Mediated Multiprong Targeting Strategy Against Breast Cancer and Tumor-Associated Macrophages: Design, Optimization, Characterization, and Cytologic Evaluation |
| title_short | CD44-Receptors-Mediated Multiprong Targeting Strategy Against Breast Cancer and Tumor-Associated Macrophages: Design, Optimization, Characterization, and Cytologic Evaluation |
| title_sort | cd44 receptors mediated multiprong targeting strategy against breast cancer and tumor associated macrophages design optimization characterization and cytologic evaluation |
| topic | paclitaxel tamoxifen hyaluronic acid polymeric nanoparticles cd44-receptors breast cancer cell uptake anticancer efficacy |
| url | https://www.dovepress.com/cd44-receptors-mediated-multiprong-targeting-strategy-against-breast-c-peer-reviewed-fulltext-article-IJN |
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