Green design “bioinspired disassembly-reassembly strategy” applied for improved tumor-targeted anticancer drug delivery

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• 作者：Ruoning Wang^a ; Xiaochen Gu^b ; Jianping Zhou^a ; ^{zhoujianp60@163.com" class="auth_mail" title="E-mail the corresponding author} ; Lingjia Shen^c ; Lifang Yin^a ; Peiying Hua^a ; Yang Ding^a ; ^{dydszyzf@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Green designed lipoprotein-like nanoparticles ; Bioinspired disassembly-reassembly strategy ; Multi-targeting system ; Enhanced anticancer efficacy ; Safety profile
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：10 August 2016
• 年：2016
• 卷：235
• 期：Complete
• 页码：134-146
• 全文大小：3021 K

文摘

In this study, a simple and green approach ‘bioinspired disassembly-reassembly strategy’ was employed to reconstitute lipoprotein nanoparticles (RLNs) using whole-components of endogenous ones (contained dehydrated human lipids and native apolipoproteins). These RLNs were engineered to mimic the configuration and properties of natural lipoproteins for efficient drug delivery. In testing therapeutic targeting to microtubules, paclitaxel (PTX) was reassembled into RLNs to achieve improved targeted anti-carcinoma treatment and minimize adverse effects, demonstrating ultimately more applicable than HDL-like particles which are based on exogenous lipid sources. We have characterized that apolipoprotein-decoration of PTX-loaded RLNs (RLNs-PTX) led to favoring uniformly dispersed distribution, increasing PTX-encapsulation with a sustained-release pattern, while enhancing biostability during blood circulation. The innate biological RLNs induced efficient intracellular trafficking of cargos in situ via multi-targeting mechanisms, including scavenger receptor class B type I (SR-BI)-mediated direct transmembrane delivery, as well as other lipoprotein-receptors associated endocytic pathways. The resulting anticancer treatment from RLNs-PTX was demonstrated a half-maximal inhibitory concentration of 0.20 μg/mL, cell apoptosis of 18.04% 24 h post-incubation mainly arresting G2/M cell cycle in vitro, and tumor weight inhibition of 70.51% in vivo. Collectively, green-step assembly-based RLNs provided an efficient strategy for mediating tumor-targeted accumulation of PTX and enhanced anticancer efficacy.