Please use this identifier to cite or link to this item:
https://hdl.handle.net/11147/14201
Title: | HER2-Targeted, Degradable Core Cross-Linked Micelles for Specific and Dual pH-Sensitive DOX Release | Authors: | Bayram, N.N. Ulu, G.T. Topuzoğulları, M. Baran, Y. Dinçer, İşoğlu, S. |
Keywords: | Cell death Controlled drug delivery Diseases Infrared spectroscopy Living polymerization Particle size Peptides pH sensors Sulfur compounds Targeted drug delivery Transmission electron microscopy Breast Cancer Cross-linked micelles Doxorubicin Dual ph-responsiveness HER2 targeting Micelle nanocarrier Multifunctional nanocarrier Nanocarriers Ph responsiveness Reversible addition-fragmentation chain transfer polymerization Micelles antineoplastic agent doxorubicin drug carrier chemistry drug release human micelle pH Antineoplastic Agents Doxorubicin Drug Carriers Drug Liberation Humans Hydrogen-Ion Concentration Micelles |
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. © 2021 Wiley-VCH GmbH | URI: | https://doi.org/10.1002/mabi.202100375 https://hdl.handle.net/11147/14201 |
ISSN: | 1616-5187 |
Appears in Collections: | PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection |
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