苯硼酸
硼酸
乙烯醇
前药
两亲性
聚合物
药物输送
右旋糖酐
纳米颗粒
甲基丙烯酸酯
材料科学
组合化学
紫杉醇
有机化学
化学
纳米技术
共聚物
生物化学
催化作用
医学
外科
化疗
作者
Wanyue Xiao,Shaoxing Sun,Rui Geng,Duohang Bi,Yijing Liu,Jintao Zhu
标识
DOI:10.1021/acsami.4c15172
摘要
Boronate ester can be used to prepare intelligent polymer nanoparticles (NPs). However, the traditional boronate ester polymer NPs made of boronic acid and diols using a "single-lock" strategy (B–O NPs) exhibit low drug loading capacity (DLC) and insufficient lysosomal escape ability, resulting in limited antitumor efficacy. We develop a "two-lock" strategy that combines dodecanamine and boronic acid using boron–nitrogen (B ← N) coordination to enhance the formation of a boronate ester polymer. Through this strategy, amphiphilic dextran and poly(vinyl alcohol) are synthesized through conjugation with the phenylboronic acid (PBA)/dodecanamine complex. The amphiphilic dextran encapsulates paclitaxel (PTX) to form B–N–O NPs with a higher DLC than their "single-lock" compartments due to enhanced boronate ester stability and improved hydrophobic drug-polymer interactions. Moreover, the B–N–O NPs release more PTX under acidic conditions compared with the B–O NPs. To demonstrate the generality of this "two-lock" strategy, eight polymer prodrug B–N–O NPs employing poly(vinyl alcohol) or dextran, along with PBA-modified gemcitabine, fluorouracil, and 7-ethyl-10-hydroxycamptothecin, or boronic acid-containing bortezomib and dodecanamine, are prepared, showing overall enhanced DLC and higher responsive drug release efficiency compared to B–O NPs. Importantly, B–N–O NPs with a combination of dodecanamine and boronic acid show a better lysosomal escape capability than B–O NPs. Moreover, B–N–O NPs exhibit stronger cytotoxicity compared to B–O NPs and free drugs in vitro. Their enhanced drug loading, responsive drug release, and lysosomal escape abilities contribute to enhanced antitumor efficacy in vivo. This "two-lock" strategy can be a general and convenient method to prepare responsive polymer NPs with enhanced anticancer efficacy.
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