Tumor-penetrating peptide modified and pH-sensitive polyplexes for tumor targeted siRNA delivery

Literature Information

Publication Date 2016-05-09
DOI 10.1039/C6PY00427J
Impact Factor 5.582
Authors

Guoyong Zhou, Yongmin Xu, Meiwan Chen, Du Cheng


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Abstract

A pH-sensitive ternary block copolymer comprising poly(ethylene glycol)methyl ether methacrylate (PEGMA), and pH-sensitive segments poly(2-(dimethylamino) ethylmethacrylate) (PDMA) and poly(2-(diisopropyl amino)ethyl methacrylate) (PDPA) (mal-PEGMA-b-PDPA-b-PDMA, PMDM) was synthesized. The copolymer effectively complexed with siRNA at pH 5.0 to form a polyplex which showed decreased positive charge along with the increase of pH value due to deprotonation of the PDPA block. The nearly non-charged polyplex at pH 7.4 exhibited enhanced stability and inertness in serum-containing media, which is favorable for a prolonged circulation time and reduced cytotoxicity. The pH-sensitivity of PDMA and PDPA also enhanced the lysosomal escape of polyplexes after endocytosis. Moreover, modification of the tumor-penetrating peptide iRGD endowed the polyplexes with effective intratumoral delivery and high transfection efficiency. A study using the luciferase expression assay achieved highly effective target gene silencing both in vitro and in vivo, which revealed the potential of our iRGD-modified and pH-sensitive siRNA polyplex as a promising siRNA delivery system in cancer treatment.

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