Tumor acidity-sensitive linkage-bridged block copolymer for therapeutic siRNA delivery

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• 作者：Cong-Fei Xu^a ; ¹ ; Hou-Bing Zhang^a ; ¹ ; Chun-Yang Sun^b ; Yang Liu^b ; Song Shen^b ; Xian-Zhu Yang^a ; ^{yangxz@mail.ustc.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Yan-Hua Zhu^b ; Jun Wang^a ; ^b ; ^c ; ^{jwang699@ustc.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：PEG detachment ; Tumor pH-responsive ; siRNA ; Cancer nanotechnology
• 刊名：Biomaterials
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：88
• 期：Complete
• 页码：48-59
• 全文大小：2989 K

文摘

The design of ideal nanoparticle delivery systems should be capable of meeting the requirements of several stages of drug delivery, including prolonged circulation, enhanced accumulation and penetration in the tumor, facilitated cellular internalization and rapid release of the active drug in the tumor cells. However, among the current design strategies, meeting the requirements of one stage often conflicts with the other. Herein, a tumor pH-labile linkage-bridged block copolymer of poly(ethylene glycol) with poly(lacide-co-glycolide) (PEG-Dlink_m-PLGA) was used for siRNA delivery to fulfill all aforementioned requirements of these delivery stages. The obtained siRNA-encapsulating PEG-Dlink_m-PLGA nanoparticle gained efficiently prolonged circulation in the blood and preferential accumulation in tumor sites via the PEGylation. Furthermore, the PEG surface layer was detached in response to the tumor acidic microenvironment to facilitate cellular uptake, and the siRNA was rapidly released within tumor cells due to the hydrophobic PLGA layer. Hence, PEG-Dlink_m-PLGA nanoparticles met the requirements of several stages of drug delivery, and resulted in the enhanced therapeutic effect of the nanoparticular delivery systems.