Suppression of tumor growth by systemic delivery of anti-VEGF siRNA with cell-penetrating peptide-modified MPEG-PCL nanomicelles

European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V
Takanori KanazawaHiroaki Okada

Abstract

Small interfering RNAs (siRNAs) have potential applications for many diseases, such as cancer, since siRNAs can specifically silence disease-associated genes. However, effective siRNA carriers need to be developed to overcome the low siRNA stability in vivo, to form stable complexes and to facilitate intracellular uptake. In this study, to develop a carrier for systemic siRNA delivery, we prepared methoxy poly(ethylene glycol) (MPEG)/polycaprolactone (PCL) diblock copolymers conjugated with a cell-penetrating peptide, Tat, via a disulfide linkage, and evaluated their ability as an siRNA carrier. The particle size of MPEG-PCL-SS-Tat/siRNA complexes was approximately 100-200 nm. The cellular uptake ability after transfection with FAM-siRNA with MPEG-PCL-SS-Tat was significantly higher than that with FAM-siRNA only. MPEG-PCL-SS-Tat did not induce substantial cytotoxicity. Intravenous injection of MPEG-PCL-SS-Tat/anti-vascular endothelial growth factor (VEGF) siRNA (siVEGF) complexes achieved a high anti-tumor effect in tumor-bearing mice. These results suggest that MPEG-PCL-SS-Tat is a potentially effective siRNA carrier for silencing genes in vitro and in vivo.

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Citations

Apr 8, 2014·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Min Hyung KangYoung Wook Choi
Aug 22, 2015·International Journal of Molecular Sciences·Hua LiWenxue Ma
Jun 6, 2014·Expert Opinion on Drug Delivery·Shun ChenWeien Yuan
Jun 9, 2016·Iranian Red Crescent Medical Journal·Moslem Jafari SaniAli Zarei Mahmudabadi
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Feb 24, 2021·ACS Applied Materials & Interfaces·Huiying XuBang-Ce Ye
Dec 12, 2020·Acta Pharmaceutica Sinica. B·Nitin Bharat CharbeFlavia C Zacconi

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