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Silver Nanoparticles Covered with pH-Sensitive Camptothecin-Loaded Polymer Prodrugs: Switchable Fluorescence “Off” or “On” and Drug Delivery Dynamics in Living Cells

Author:
Qiu, Liang, Li, Jia-Wei, Hong, Chun-Yan, Pan, Cai-Yuan
Source:
ACS applied materials & interfaces 2017 v.9 no.46 pp. 40887-40897
ISSN:
1944-8252
Subject:
cytotoxicity, drug delivery systems, drugs, energy transfer, fluorescence, human cell lines, in vitro studies, lysosomes, nanoparticles, nanosilver, neoplasms, pH, polymerization, polymers
Abstract:
A unique drug delivery system, in which silver nanoparticles (AgNPs) are covered with camptothecin (CPT)-based polymer prodrug, has been developed, and the polymer prodrug, in which the CPT is linked to the polymer side chains via an acid-labile β-thiopropionate bond, is prepared by RAFT polymerization. For poly(2-(2-hydroxyethoxy)ethyl methacrylate-co-methacryloyloxy-3-thiahexanoyl-camptothecin)@AgNPs [P(HEO₂MA-co-MACPT)@AgNPs], the polymer thickness on the AgNP surface is around 5.9 nm (TGA method). In vitro tests in buffer solutions at pH = 7.4 reveal that fluorescence of the CPT in the hybrid nanoparticles is quenched due to the nanoparticle surface energy transfer (NSET) effect, but under acidic conditions, the CPT fluorescence is gradually recovered with gradual release of the CPT molecules from the hybrid nanoparticles through cleavage of the acid-labile bond. The NSET “on” and “off” is induced by the CPT–AgNP distance change. This unique property makes it possible to track the CPT delivery and release process from the hybrid nanoparticles in the living cells in a real-time manner. The internalization and intracellular releasing tests of the hybrid nanoparticles in the HeLa cells demonstrate that the lysosome containing the hybrid nanoparticles displays CPT blue fluorescence due to release of the CPT under acidic conditions, and the drug-releasing kinetics shows fluorescence increase of the released CPT with incubation time. The cytotoxicity of hybrid nanoparticles is dependent on activity of the acid-labile bond. Therefore, this is a potential efficient drug delivery system in cancer therapy and a useful approach to study the mechanism of release process in the cells.
Agid:
5863906