1. Carboxylated chitosan-mediated improved efficacy of mesoporous silica nanoparticle-based targeted drug delivery system for breast cancer therapy.
- Author
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Lohiya G and Katti DS
- Subjects
- Antibiotics, Antineoplastic chemistry, Breast Neoplasms pathology, Cell Proliferation drug effects, Dose-Response Relationship, Drug, Doxorubicin chemistry, Drug Screening Assays, Antitumor, Female, Humans, Hydrogen-Ion Concentration, Molecular Structure, Particle Size, Porosity, Structure-Activity Relationship, Surface Properties, Antibiotics, Antineoplastic pharmacology, Breast Neoplasms drug therapy, Chitosan chemistry, Doxorubicin pharmacology, Drug Delivery Systems, Nanoparticles chemistry, Silicon Dioxide chemistry
- Abstract
Nanoparticle-based targeting of overexpressed cell-surface receptors is a promising strategy that provides precise delivery of drugs to cancer cells. In the present study, we developed highly reproducible and monodispersed, chitosan-coated (pH-responsive), doxorubicin-loaded, aptamer-mesoporous silica nanoparticle (MSN) bioconjugates for actively targeting breast cancer cells harboring overexpression of EGF receptors (EGFR/HER2). The developed targeted MSNs demonstrated higher uptake and cytotoxicity of triple negative and HER2 positive breast cancer cells when compared to non-targeted MSNs. The chitosan coating imparted pH-responsiveness and endo/lysosomal escape ability to MSNs, which augmented cytosolic delivery of an anticancer drug. Partial carboxylation of chitosan coated on MSNs allowed for a greater release of drug in a shorter duration of time while retaining pH-responsiveness and endo/lysosomal escape ability. Overall, the coating of carboxylated-chitosan over MSNs enabled tunable drug release kinetics, conjugation of aptamers (targeting agents), and endo/lysosomal escape which together significantly enhanced the efficacy of the developed drug delivery system., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2022
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