Development of small interfering RNA delivery system using PEI-PEG-APRPG polymer for antiangiogenic vascular endothelial growth factor tumor-targeted therapy

Zong-Xia Lu1, Li-Ting Liu1,2, Xian-Rong Qi11Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People&#39;s Republic of China; 2Department of Pharmacy, School and Hospital of Stomatology, Peking University, Beijing, People&#39;s Republic of Ch...

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Autores principales:	Lu ZX, Liu LT, Qi XR
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/e80a956fccd84123a084e40bd539add3
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spelling	oai:doaj.org-article:e80a956fccd84123a084e40bd539add32021-12-02T02:42:29ZDevelopment of small interfering RNA delivery system using PEI-PEG-APRPG polymer for antiangiogenic vascular endothelial growth factor tumor-targeted therapy1176-91141178-2013https://doaj.org/article/e80a956fccd84123a084e40bd539add32011-08-01T00:00:00Zhttp://www.dovepress.com/development-of-small-interfering-rna-delivery-system-using-pei-peg-apr-a8068https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Zong-Xia Lu1, Li-Ting Liu1,2, Xian-Rong Qi11Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People&#39;s Republic of China; 2Department of Pharmacy, School and Hospital of Stomatology, Peking University, Beijing, People&#39;s Republic of ChinaBackground: Small interfering RNA (siRNA) can silence target genes in the cytoplasm and be a major tool in gene therapy. Vascular endothelial growth factor (VEGF), a potent regulator of angiogenesis, is overexpressed in most tumors and is closely associated with tumor growth and metastasis. It has been shown that inhibition of VEGF expression by siRNA is an effective and useful method for antiangiogenic tumor therapy.Methods: In the present study, we synthesized a targeted delivery system of PEI-PEG-APRPG incorporating angiogenic vessel-homing Ala-Pro-Arg-Pro-Gly (APRPG) peptide into cationic polyethylenimine (PEI) via a hydrophilic poly(ethylene glycol) (PEG) spacer.Results: PEI-PEG-APRPG effectively condensed siRNA into 20&ndash;50 nm nanoparticles with a positive surface charge using a suitable N/P ratio. The siRNA/PEI-PEG-APRPG complex effectively enhanced the stability of siRNA in RNase A, and improved the proliferation-inhibiting ability and transfection efficiency of siRNA in vitro and tumor accumulation in vivo. In addition, the siRNA/PEI-PEG-APRPG complex exhibited high efficiency as antitumor therapy with regard to tumor growth, microvessel density, and VEGF protein and mRNA levels.Conclusion: These findings suggest that PEI-PEG-APRPG effectively delivers siRNA to tumors overexpressing VEGF and thereby inhibits tumor growth.Keywords: PEI-PEG-APRPG, VEGF siRNA, gene delivery, tumor-targeted, antiangiogenic therapyLu ZXLiu LTQi XRDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 1661-1673 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Lu ZX Liu LT Qi XR Development of small interfering RNA delivery system using PEI-PEG-APRPG polymer for antiangiogenic vascular endothelial growth factor tumor-targeted therapy
description	Zong-Xia Lu1, Li-Ting Liu1,2, Xian-Rong Qi11Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People&#39;s Republic of China; 2Department of Pharmacy, School and Hospital of Stomatology, Peking University, Beijing, People&#39;s Republic of ChinaBackground: Small interfering RNA (siRNA) can silence target genes in the cytoplasm and be a major tool in gene therapy. Vascular endothelial growth factor (VEGF), a potent regulator of angiogenesis, is overexpressed in most tumors and is closely associated with tumor growth and metastasis. It has been shown that inhibition of VEGF expression by siRNA is an effective and useful method for antiangiogenic tumor therapy.Methods: In the present study, we synthesized a targeted delivery system of PEI-PEG-APRPG incorporating angiogenic vessel-homing Ala-Pro-Arg-Pro-Gly (APRPG) peptide into cationic polyethylenimine (PEI) via a hydrophilic poly(ethylene glycol) (PEG) spacer.Results: PEI-PEG-APRPG effectively condensed siRNA into 20&ndash;50 nm nanoparticles with a positive surface charge using a suitable N/P ratio. The siRNA/PEI-PEG-APRPG complex effectively enhanced the stability of siRNA in RNase A, and improved the proliferation-inhibiting ability and transfection efficiency of siRNA in vitro and tumor accumulation in vivo. In addition, the siRNA/PEI-PEG-APRPG complex exhibited high efficiency as antitumor therapy with regard to tumor growth, microvessel density, and VEGF protein and mRNA levels.Conclusion: These findings suggest that PEI-PEG-APRPG effectively delivers siRNA to tumors overexpressing VEGF and thereby inhibits tumor growth.Keywords: PEI-PEG-APRPG, VEGF siRNA, gene delivery, tumor-targeted, antiangiogenic therapy
format	article
author	Lu ZX Liu LT Qi XR
author_facet	Lu ZX Liu LT Qi XR
author_sort	Lu ZX
title	Development of small interfering RNA delivery system using PEI-PEG-APRPG polymer for antiangiogenic vascular endothelial growth factor tumor-targeted therapy
title_short	Development of small interfering RNA delivery system using PEI-PEG-APRPG polymer for antiangiogenic vascular endothelial growth factor tumor-targeted therapy
title_full	Development of small interfering RNA delivery system using PEI-PEG-APRPG polymer for antiangiogenic vascular endothelial growth factor tumor-targeted therapy
title_fullStr	Development of small interfering RNA delivery system using PEI-PEG-APRPG polymer for antiangiogenic vascular endothelial growth factor tumor-targeted therapy
title_full_unstemmed	Development of small interfering RNA delivery system using PEI-PEG-APRPG polymer for antiangiogenic vascular endothelial growth factor tumor-targeted therapy
title_sort	development of small interfering rna delivery system using pei-peg-aprpg polymer for antiangiogenic vascular endothelial growth factor tumor-targeted therapy
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/e80a956fccd84123a084e40bd539add3
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Development of small interfering RNA delivery system using PEI-PEG-APRPG polymer for antiangiogenic vascular endothelial growth factor tumor-targeted therapy

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