Sialic Acid-Targeted Nanovectors with Phenylboronic Acid-Grafted Polyethylenimine Robustly Enhance siRNA-Based Cancer Therapy

	Sialic Acid-Targeted Nanovectors with Phenylboronic Acid-Grafted Polyethylenimine Robustly Enhance siRNA-Based Cancer Therapy
	Ji, Manyi; Li, Ping; Sheng, Nan; Liu, Lanlan; Pan, Hong; Wang, Ce; Cai, Lintao; Ma, Yifan
刊名	ACS APPLIED MATERIALS & INTERFACES
	2016
英文摘要	Small interference RNA (siRNA)-based therapy holds great potential for cancer treatment. However, its clinical application remains unsatisfied due to the lack of a safe and effective RNA delivery system. Aberrantly elevated sialyation on cell membrane has been reported as an attractive target for cancerdiagnosis and therapy. In this study, phenylboronic acid (PBA) was conjugated onto low molecular weightpolyethylenimine (PEI1.8k) to generate amphiphilic PBA-grafted PEI1.8k (PEI-PBA) nanovector, which was designed to facilitate cancer targeted RNA delivery through the recognition of sialic structures on a cancercell membrane. PEI-PBA simultaneously encapsulated siRNA to form PEI-PBA/siRNA nanocomplexes withgreat biocompatibility, serum stability and RNase resistance. The cell culture study showed that PEI-PBA/siRNA dramatically increased siRNA uptake up to 70-90% in several cancer cell lines, which relied on the interaction between PBA and sialic acid on cell membrane. Moreover, the PEI-PBA nanovector effectively promoted the lysosome escape of siRNA, decreasing the expression of target gene Polo-like kinase (PLK-1) in cancer cells. The systemic administration of PEI-PBA/PLK-1 siRNA (PEI-PBA/siPLK1) nanocomplexes not only facilitated tumor-targeted siRNA delivery but also significantly decreased PLK-1 expression in tumors, thereby robustly inducing tumor apoptosis and cell cycle arrest. Additionally, the administration of PEI-PBA/siPLK1 did not cause significant systemic toxicity or immunotoxicity. Hence,sialic acid-targeted PEI-PBA could be a highly efficient and safe nanovector to improve the efficacy ofcancer siRNA therapy.
收录类别	SCI
原文出处	http://pubs.acs.org/doi/abs/10.1021/acsami.5b11866
语种	英语
内容类型	期刊论文
源URL	[http://ir.siat.ac.cn:8080/handle/172644/10650]
专题	深圳先进技术研究院_医药所
作者单位	ACS APPLIED MATERIALS & INTERFACES
推荐引用方式 GB/T 7714	Ji, Manyi,Li, Ping,Sheng, Nan,et al. Sialic Acid-Targeted Nanovectors with Phenylboronic Acid-Grafted Polyethylenimine Robustly Enhance siRNA-Based Cancer Therapy[J]. ACS APPLIED MATERIALS & INTERFACES,2016.
APA	Ji, Manyi.,Li, Ping.,Sheng, Nan.,Liu, Lanlan.,Pan, Hong.,...&Ma, Yifan.(2016).Sialic Acid-Targeted Nanovectors with Phenylboronic Acid-Grafted Polyethylenimine Robustly Enhance siRNA-Based Cancer Therapy.ACS APPLIED MATERIALS & INTERFACES.
MLA	Ji, Manyi,et al."Sialic Acid-Targeted Nanovectors with Phenylboronic Acid-Grafted Polyethylenimine Robustly Enhance siRNA-Based Cancer Therapy".ACS APPLIED MATERIALS & INTERFACES (2016).