Hypoxia-Sensitive Zwitterionic Vehicle for Tumor-Specific Drug Delivery through Antifouling-Based Stable Biotransport Alongside PDT-Sensitized Controlled Release.
Hypoxia-Sensitive Zwitterionic Vehicle for Tumor-Specific Drug Delivery through Antifouling-Based Stable Biotransport Alongside PDT-Sensitized Controlled Release.
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DOI：
10.1021/acs.biomac.1c00301
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发表时间：
2021-04
影响因子：
6.2
通讯作者：
Tingjie Yin;Xuxin Chu;Jiejie Cheng;Jinlai Liang;Jianping Zhou;Meirong Huo
中科院分区：
文献类型：
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作者：
Tingjie Yin;Xuxin Chu;Jiejie Cheng;Jinlai Liang;Jianping Zhou;Meirong Huo
DHigh-PEI-(A+P)是一种低氧敏感的两性离子载体，具有抗污染、稳定的生物传输和光动力疗法(PDT)敏化的低氧响应时空可控药物释放的能力，可用于肿瘤特异性的化疗药物和生物大分子的输送。由甜菜碱单体(DMAAPS)、光敏剂(PpIX)和偶氮苯-4，4‘-二元酸修饰的聚乙烯亚胺组成了两亲性DHigh-PEI-(A+P)。本文选择紫杉醇(PTX)作为常用的模型药物来验证所设计的聚合物的功能。首先，DHigh-PEI-(A+P)在高载药量(~gt；35%)的水溶液中与PTX自发共组装。DHigh-PEI-(A+P)理想的抗污染能力独立于血清中有效的4T1内吞作用和全身肿瘤靶向来验证。此外，PPIX介导的PDT被证实在细胞和组织水平上加重和均质低氧微环境，从而迅速响应地分解DHigh-PEI-(A+P)，从而以良好控制的方式强劲地释放药物。结果，DHigh-PEI-(A+P)增强了PTX对原位4T1小鼠模型的治疗效果，附带损害最小。我们认为DHigh-PEI-(A+P)可以作为一种特制的通用载体，用于肿瘤特异性给药，具有不同的物理化学性质。
A hypoxia-sensitive zwitterionic vehicle, DHigh-PEI-(A+P), with the ability for antifouling-mediated, stable biotransport and a photodynamic therapy (PDT)-sensitized hypoxic response for spatiotemporal controlled drug release, was developed for the tumor-specific delivery of chemotherapeutics and biomacromolecules. The amphiphilic DHigh-PEI-(A+P) was constructed from a betaine monomer (DMAAPS), a photosensitizer (PpIX), and an azobenzene-4,4'-dicarboxylic acid-modified polyethylenimine. Herein paclitaxel (PTX) was selected as a common model drug to verify the functions of the designed polymer. First, DHigh-PEI-(A+P) was demonstrated to spontaneously coassemble with PTX in aqueous solution with high drug loading (>35%). The desirable antifouling ability of DHigh-PEI-(A+P) was independently verified by efficient 4T1 endocytosis in serum alongside systemic tumor targeting. Furthermore, PpIX-mediated PDT was verified to aggravate and homogenize a hypoxic microenvironment at the cell and tissue levels for a sharp responsive disassembly of DHigh-PEI-(A+P) and thus a robust drug release in a well-controlled manner. As a result, DHigh-PEI-(A+P) amplified the therapeutic outcome of PTX on orthotopic 4T1 mouse models with minimal collateral damage. We proposed that DHigh-PEI-(A+P) may serve as a tailor-designed universal vehicle for the tumor-specific delivery of drugs with distinct physicochemical properties.