National Engineering Research Center for Nanomedicine, College of Life Science and Technology , Huazhong University of Science and Technology , 430074 , Wuhan , China.
Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica , Huazhong University of Science and Technology , 430074 Wuhan , China.
ACS Appl Mater Interfaces. 2020 Feb 19;12(7):7995-8005. doi: 10.1021/acsami.9b22654. Epub 2020 Feb 10.
The combination of photothermal therapy (PTT) with chemotherapy has great potential to maximize the synergistic effect of thermo-induced chemosensitization and improve treatment performance. To achieve high drug-loading capacity as well as precise synchronization between the controllable release of chemotherapeutics and the duration of near-infrared PTT, in this work, a facile one-step method was first developed to fabricate a novel injectable in situ forming photothermal modulated hydrogel drug delivery platform (D-PPy@PNAs), in which a PNIPAM-based temperature-sensitive acidic triblock polymer [poly(acrylic acid---isopropylamide--acrylic acid (PNA)] was utilized as the stabilizing agent in the polymerization of polypyrrole (PPy). The in situ forming hydrogels showed a sensitive temperature-responsive sol-gel phase-transition behavior, as well as an excellent photothermal property. The strong interaction of ionic bonds together with π-π stacking interactions resulted in high doxorubicin (DOX) loading capacity and controlled/sustained drug release behavior. In addition, D-PPy@PNAs also displayed enhanced cellular uptake and promoted intratumoral penetration of DOX upon NIR laser irradiation. The synergistic photothermal therapy-chemotherapy of D-PPy@PNA hydrogels greatly improved the antitumor efficacy in vivo. Therefore, thermosensitive polypyrrole-based D-PPy@PNA hydrogels may be powerful drug delivery nanoplatforms for precisely synergistic photothermo-chemotherapy of tumors.
光热治疗（PTT）与化学疗法相结合具有很大的潜力，可以最大限度地提高热诱导化疗增敏的协同效应，提高治疗效果。为了实现高载药能力以及化疗药物可控释放与近红外 PTT 持续时间之间的精确同步，在这项工作中，首次开发了一种简便的一步法来制备新型可注射原位形成光热调制水凝胶药物输送平台（D-PPy@PNAs），其中聚异丙基丙烯酰胺基温敏性酸性三嵌段聚合物[聚（丙烯酸---异丙基酰胺---丙烯酸（PNA）]被用作聚合吡咯（PPy）的稳定剂。原位形成的水凝胶表现出敏感的温度响应溶胶-凝胶相转变行为以及优异的光热性能。离子键的强相互作用以及π-π堆积相互作用导致高阿霉素（DOX）载药能力和控制/持续的药物释放行为。此外，在近红外激光照射下，D-PPy@PNAs 还表现出增强的细胞摄取和促进 DOX 的肿瘤内渗透。D-PPy@PNA 水凝胶的协同光热化疗极大地提高了体内抗肿瘤疗效。因此，基于热敏性聚吡咯的 D-PPy@PNA 水凝胶可能是用于精确协同光热化疗肿瘤的强大药物输送纳米平台。
