Pancreatic cancer therapy by systemic administration of VEGF siRNA contained in calcium phosphate/charge-conversional polymer hybrid nanoparticles

Journal of Controlled Release : Official Journal of the Controlled Release Society
Frederico PittellaKazunori Kataoka

Abstract

Development of an efficient in vivo delivery vehicle of small interfering RNA (siRNA) is the key challenge for successful siRNA-based therapies. In this study, toward systemic delivery of siRNA to solid tumors, a smart polymer/calcium phosphate (CaP)/siRNA hybrid nanoparticle was prepared to feature biocompatibility, reversible stability and endosomal escape functionality using a pH sensitive block copolymer of poly(ethylene glycol) and charge-conversional polymer (PEG-CCP), of which anionic functional groups could be converted to cationic groups in an endosomal acidic condition for facilitated endosomal escape. Nanoparticles were confirmed to be approximately 100nm in size, narrowly dispersed and spherical. Also, the nanoparticle was highly tolerable in medium containing serum, while releasing the entrapped siRNA in a cytoplasm-mimicking ionic condition, presumably based on the equilibrium between CaP complexes and calcium ions. Further, the nanoparticle showed high gene silencing efficiency in cultured pancreatic cancer cells (BxPC3) without associated cytotoxicity. Ultimately, systemic administration of the nanoparticles carrying vascular endothelium growth factor (VEGF) siRNA led to the significant reduction in the subcutan...Continue Reading

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Nov 16, 2013·Therapeutic Delivery·James B DelehantyIgor L Medintz
Jul 6, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Min Sang LeeJi Hoon Jeong
Nov 27, 2014·Expert Opinion on Drug Delivery·Luís NovoWim E Hennink
Jul 6, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Horacio Cabral, Kazunori Kataoka
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Feb 20, 2014·Advanced Healthcare Materials·Fei-Fei AnXing-Jie Liang
Nov 12, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Peng MiKazunori Kataoka
Jan 21, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Frederico PittellaKazunori Kataoka
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Jan 23, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·David VetvickaDavid Oupický
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Jun 30, 2016·Advanced Drug Delivery Reviews·Hyun Jin KimKazunori Kataoka
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