HER2-Specific Peptide Targeted Core Cross-Linked Micelles for Breast Cancer: A Comparative Study

This study aims to prepare a novel breast cancer-targeted micelle-based nanocarrier, which is stable in circulation, allowing intracellular drug release, and to investigate its cytotoxicity, apoptosis, and cytostatic effects, in vitro. The shell part of the micelle is composed of zwitterionic sulfob...

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Bibliographic Details
Published in:Pharmaceutics 2023-02, Vol.15 (3)
Main Authors: Bayram, Nazende Nur, Ulu, Gizem Tuğçe, Abdulhadi, Nusaibah Abdulsalam, Gürdap, Seda, İşoğlu, İsmail Alper, Baran, Yusuf, İşoğlu, Sevil Dinçer
Format: Article
Language:English
Subjects:
Antibodies
Comparative analysis
Drug delivery systems
Drugs
Identification and classification
Materials
Micelles
Peptides
Vehicles
Viral antibodies
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Summary:This study aims to prepare a novel breast cancer-targeted micelle-based nanocarrier, which is stable in circulation, allowing intracellular drug release, and to investigate its cytotoxicity, apoptosis, and cytostatic effects, in vitro. The shell part of the micelle is composed of zwitterionic sulfobetaine ((N-3-sulfopropyl-N,N-dimethylamonium)ethyl methacrylate), while the core part is formed by another block, consisting of AEMA (2-aminoethyl methacrylamide), DEGMA (di(ethylene glycol) methyl ether methacrylate), and a vinyl-functionalized, acid-sensitive cross-linker. Following this, a targeting agent (peptide (LTVSPWY) and antibody (Herceptin[sup.®] )), in varying amounts, were coupled to the micelles, and they were characterized by [sup.1] H NMR, FTIR (Fourier-transform infrared spectroscopy), Zetasizer, BCA protein assay, and fluorescence spectrophotometer. The cytotoxic, cytostatic, apoptotic, and genotoxic effects of doxorubicin-loaded micelles were investigated on SKBR-3 (human epidermal growth factor receptor 2 (HER2)-positive) and MCF10-A (HER2-negative). According to the results, peptide-carrying micelles showed a higher targeting efficiency and better cytostatic, apoptotic, and genotoxic activities than antibody-carrying and non-targeted micelles. Also, micelles masked the toxicity of naked DOX on healthy cells. In conclusion, this nanocarrier system has great potential to be used in different drug-targeting strategies, by changing targeting agents and drugs.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics15030733