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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