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https://hdl.handle.net/11147/11887
Title: | Her2-Targeted, Degradable Core Cross-Linked Micelles for Specific and Dual Ph-Sensitive Dox Release | Authors: | Bayram, Nazende Nur Ulu, Gizem Tuğçe Topuzoğulları, Murat Baran, Yusuf Dinçer İşoğlu, Sevil |
Keywords: | Micelle nanocarriers Breast cancer Cross-linked micelles RAFT polymerization HER2 targeting |
Publisher: | John Wiley and Sons Inc. | Abstract: | Here, a targeted, dual-pH responsive, and stable micelle nanocarrier is designed, which specifically selects an HER2 receptor on breast cancer cells. Intracellularly degradable and stabilized micelles are prepared by core cross-linking via reversible addition-fragmentation chain-transfer (RAFT) polymerization with an acid-sensitive cross-linker followed by the conjugation of maleimide-doxorubicin to the pyridyl disulfide-modified micelles. Multifunctional nanocarriers are obtained by coupling HER2-specific peptide. Formation of micelles, addition of peptide and doxorubicin (DOX) are confirmed structurally by spectroscopical techniques. Size and morphological characterization are performed by Zetasizer and transmission electron microscope (TEM). For the physicochemical verification of the synergistic acid-triggered degradation induced by acetal and hydrazone bond degradation, Infrared spectroscopy and particle size measurements are used. Drug release studies show that DOX release is accelerated at acidic pH. DOX-conjugated HER2-specific peptide-carrying nanocarriers significantly enhance cytotoxicity toward SKBR-3 cells. More importantly, no selectivity toward MCF-10A cells is observed compared to HER2(+) SKBR-3 cells. Formulations cause apoptosis depending on Bax and Caspase-3 and cell cycle arrest in G2 phase. This study shows a novel system for HER2-targeted therapy of breast cancer with a multifunctional nanocarrier, which has higher stability, dual pH-sensitivity, selectivity, and it can be an efficient way of targeted anticancer drug delivery. | Description: | This work was supported by the Scientific and Technological Research Council of Turkey (TÜBİTAK), Project Number: 116R057. N.N.B. and G.T.U. were supported by TÜBİTAK 116R057. | URI: | https://doi.org/10.1002/mabi.202100375 https://hdl.handle.net/11147/11887 |
ISSN: | 1616-5187 |
Appears in Collections: | Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection |
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Macromolecular Bioscience - 2021.pdf Until 2025-01-01 | Article (Makale) | 5.01 MB | Adobe PDF | View/Open Request a copy |
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