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首页> 外文期刊>ACS applied materials & interfaces >Zwitterionic Phosphorylcholine-TPE Conjugate for pH-Responsive Drug Delivery and AIE Active Imaging
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Zwitterionic Phosphorylcholine-TPE Conjugate for pH-Responsive Drug Delivery and AIE Active Imaging

机译：两性离子磷酸胆碱-TPE共轭物，用于pH响应药物递送和AIE主动成像

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摘要

Polymeric micelles have emerged as a promising nanoplatform for cancer theranostics. Herein, we developed doxorubicin (DOX) encapsulated pH-responsive polymeric micelles for combined aggregation induced emission (ME) imaging and chemotherapy. The novel zwitterionic copolymer poly(2-methacryloyloxyethylphosphorylcholine-co-2-(4-formylphenoxy)ethyl methacrylate) (poly(MPC-co-FPEMA)) was synthesized via RAFT polymerization and further converted to PMPC-hyd-TPE after conjugation of tetraphenylethene (TPE, a typical AIE chromophore) via acid-cleavable hydrazone bonds. The AIE activatable copolymer PMPC-hyd-TPE could self-assemble into spherical PC-hyd-TPE micelles, and DOX could be loaded through hydrophobic interactions. The zwitterionic micelles exhibited excellent physiological stability and low protein adsorption due to the stealthy phosphorylcholine (PC) shell. In addition, the cleavage of hydrophobic TPE molecules under acidic conditions could induce swelling of micelles, which was verified by size changes with time at pH 5.0. The in vitro DOX release profile also exhibited accelerated release rate with pH value decreasing from 7.4 to 5.0. Fluorescent microscopy and flow cytometry studies further demonstrated fast internalization and accumulation of drug loaded PC-hyd-TPE-DOX micelles in HepG2 cells, resulting in considerable time/dose-dependent cytotoxicity. Meanwhile, high-quality ME imaging of PC-hyd-TPE micelles was confirmed in HepG2 cells. Notably, ex vivo imaging study exhibited efficient accumulation and drug release of PC-hyd-TPE-DOX micelles in the tumor tissue. Consequently, the multifunctional micelles with combined nonfouling surface, ME active imaging, and pH-responsive drug delivery showed great potential as novel nanoplatforms for a new generation of cancer theranostics.
机译：高分子胶束已成为一种有前途的用于癌症治疗的纳米平台。在这里，我们开发了阿霉素（DOX）封装的pH响应型聚合物胶束，用于组合的聚集诱导发射（ME）成像和化学疗法。通过RAFT聚合反应合成了新型两性离子共聚物聚（2-甲基丙烯酰氧基乙基磷酰胆碱-甲基-2-（4-甲酰基苯氧基）乙基甲基丙烯酸酯）（聚（MPC-co-FPEMA）），并在四苯乙烯的结合后进一步转化为PMPC-hyd-TPE （TPE，一种典型的AIE生色团）通过酸可裂解的bonds键。 AIE活化共聚物PMPC-hyd-TPE可以自组装成球形PC-hyd-TPE胶束，并且DOX可以通过疏水相互作用负载。由于隐蔽的磷酸胆碱（PC）壳，两性离子胶束表现出出色的生理稳定性和低蛋白吸附。此外，疏水性TPE分子在酸性条件下的裂解可诱导胶束膨胀，这在pH 5.0时随时间变化而得到证实。体外DOX释放曲线也显示出加速释放速率，pH值从7.4降低到5.0。荧光显微镜和流式细胞术研究进一步证明，载药的PC-hyd-TPE-DOX胶束在HepG2细胞中快速内在化和蓄积，导致相当长的时间/剂量依赖性细胞毒性。同时，在HepG2细胞中证实了PC-hyd-TPE胶束的高质量ME成像。值得注意的是，离体成像研究显示肿瘤组织中PC-hyd-TPE-DOX胶束的有效积累和药物释放。因此，具有不结垢表面，ME活性成像和pH响应药物传递相结合的多功能胶束，作为新型纳米平台，在新一代癌症治疗学中显示出巨大潜力。

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