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PH and Thermal Dual-Responsive Nanoparticles for Controlled Drug Delivery with High Loading Content.

ABSTRACT: A pH and thermal dual-responsive nanocarrier with silica as the core and block copolymer composed of poly(methacrylic acid) (PMAA) and poly(N-isopropylacrylamide) (PNIPAM) as the shell was prepared by surface-initiated reversible addition-fragmentation chain-transfer (SI-RAFT) polymerization. The resulting SiO₂-PMAA-b-PNIPAM particles dispersed individually in an aqueous solution at a high pH and a low temperature but reversibly agglomerated under acidic conditions or at elevated temperatures. These dual-responsive nanoparticles were used as carriers to deliver the model drug doxorubicin (DOX) with unusually high entrapment efficiency and loading content, which is due to the small size (15 nm), light weight of the cores, and high graft density (0.619 chains/nm²) achieved by SI-RAFT polymerization. The release rate was controlled by both the pH and temperature of the surrounding medium. Moreover, these particles selectively precipitated at acidic conditions with increased temperature, which may enhance their ability to accumulate at tumor sites. Cytotoxicity studies demonstrated that DOX-loaded nanoparticles are highly active against Hela cells and more effective than free DOX of an equivalent dose. A cellular uptake study revealed that SiO₂-PMAA-b-PNIPAM nanoparticles could successfully deliver DOX molecules into the nuclei of Hela cells. All these features indicated that SiO₂-PMAA-b-PNIPAM nanoparticles are a promising candidate for therapeutic applications.

SUBMITTER: Zheng Y

PROVIDER: S-EPMC6044946 | biostudies-literature |

REPOSITORIES: biostudies-literature

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