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Targeted and redox-responsive drug delivery systems based on carbonic anhydrase IX-decorated mesoporous silica nanoparticles for cancer therapy
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Targeted and redox-responsive drug delivery systems based on carbonic anhydrase IX-decorated mesoporous silica nanoparticles for cancer therapy
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Journal Article
Targeted and redox-responsive drug delivery systems based on carbonic anhydrase IX-decorated mesoporous silica nanoparticles for cancer therapy
2020
Overview
In this work, we developed a new antibody-targeted and redox-responsive drug delivery system “MSNs-CAIX” by binding the anti-carbonic anhydrase IX antibody (A-CAIX Ab) on the surface of mesoporous silica nanoparticles (MSNs) via disulfide linkages. The design of the composite particles “MSNs-CAIX” involved the synthesis and surface functionalization with thiol groups, 2,2′-dipyridyl disulfide and CAIX antibody. In vitro, CAIX capping the doxorubicin hydrochloric (DOX)-loaded nanoparticles (DOX@MSNs-CAIX) exhibited effectively redox-responsive release in the presence of glutathione (GSH) owing to the cleavage of the disulfide bond. Compared with CAIX negative Mef cells (mouse embryo fibroblast), remarkably more DOX@MSNs-CAIX was internalized into CAIX positive 4T1 cells (mouse breast cancer cells) by receptor-mediation. Tumor targeting in vivo studies clearly demonstrated DOX@MSNs-CAIX accumulated in tumors and induced more tumor cells apoptosis in 4T1 tumor-bearing mice. With great potential, this drug delivery system is a promising candidate for targeted and redox-responsive cancer therapy.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Antibodies, Anti-Idiotypic - chemistry
/ Antibodies, Anti-Idiotypic - pharmacology
/ Carbonic Anhydrase IX - antagonists & inhibitors
/ Carbonic Anhydrase IX - immunology
/ Humanities and Social Sciences
/ Humans
/ Immunoconjugates - pharmacology
/ Metal Nanoparticles - chemistry
/ Mice
/ Oxidation-Reduction - drug effects
/ Porosity
/ Science
/ Silica
/ Tumors
