State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, ‡Key Laboratory of Advanced Materials of Ministry of Education of China, School of Materials Science and Engineering, and §Department of Chemistry, Center for Frontier Polymer Research, Tsinghua University , Beijing 100084, P. R. China.
ACS Appl Mater Interfaces. 2016 Sep 21;8(37):24445-54. doi: 10.1021/acsami.6b07669. Epub 2016 Sep 7.
Mild hyperthermia has shown great advantages when combined with chemotherapy. The development of a multifunctional platform for the integration of mild hyperthermia capability into a drug-loading system is a key issue for cancer multimodality treatment application. Herein, a facile one-pot in situ fabrication protocol of docetaxel (DTX)-loaded poly(lactic-co-glycolic acid) (PLGA)/polypyrrole (PPy) nanocomposites was developed. While the PLGA nanoparticles (NPs) allow efficient drug loading, the PPy nanobulges embedded within the surface of the PLGA NPs, formed by in situ pyrrole polymerization without the introduction of other template agents, can act as ideal mediators for photoinduced mild hyperthermia. Physiochemical characterizations of the as-prepared nanocomposites, including structure, morphology, photothermal effects, and an in vitro drug release profile, were systematically investigated. Further, 2-deoxyglucose-terminated poly(ethylene glycol) (PEG) was anchored onto the surface of the nanocomposites to endow the nanoplatform with targeting ability to tumor cells, which resulted in a 17-fold increase of NP internalization within human breast cancer cells (MCF-7) as competed with PEG-modified nanocomposites. Mild hyperthermia can be successfully mediated by the nanoplatform, and the temperature can be conveniently controlled by careful modulation of the PPy contents within the nanocomposites or the laser power density. Importantly, we have demonstrated that MCF-7 cells, which are markedly resistant to heat treatment of traditional water-bath hyperthermia, became sensitive to the PLGA/PPy nanocomposite-mediated photothermal therapy under the same mild-temperature hyperthermia. Moreover, DTX-loaded PLGA/PPy-nanocomposite-induced mild hyperthermia can strongly enhance drug cytotoxicity to MCF-7 cells. Under the same thermal dose, photoinduced hyperthermia can convert the interaction between hyperthermia and drug treatment from interference to synergism. This is the first report on the one-pot synthesis of PLGA/PPy nanocomposites by in situ pyrrole polymerization, and such a multifunctional nanoplatform is demonstrated as a high-potential agent for photoinduced mild hyperthermia and enhanced chemotherapy.
温和升温与化疗联合显示出巨大优势。将温和升温功能集成到载药系统中的多功能平台的发展是癌症多模式治疗应用的关键问题。在此，开发了一种简便的一锅原位制备载多西紫杉醇（DTX）的聚乳酸-羟基乙酸共聚物（PLGA）/聚吡咯（PPy）纳米复合材料的方法。PLGA 纳米粒（NPs）允许高效载药，而原位吡咯聚合形成的嵌入在 PLGA NPs 表面的 PPy 纳米凸块（无引入其他模板剂），可以作为光诱导温和升温的理想介体。系统研究了所制备的纳米复合材料的物理化学性质，包括结构、形态、光热效应和体外药物释放曲线。进一步，将 2-脱氧葡萄糖封端的聚乙二醇（PEG）接枝到纳米复合材料的表面，赋予纳米平台对肿瘤细胞的靶向能力，与 PEG 修饰的纳米复合材料相比，人乳腺癌细胞（MCF-7）内的 NP 内化增加了 17 倍。纳米平台可以成功介导温和升温，并且可以通过仔细调节纳米复合材料中的 PPy 含量或激光功率密度来方便地控制温度。重要的是，我们已经证明，与传统水浴升温的热疗相比，对 MCF-7 细胞，温和升温下的 PLGA/PPy 纳米复合材料介导的光热疗法变得敏感。此外，载多西紫杉醇的 PLGA/PPy-纳米复合材料诱导的温和升温可以强烈增强 MCF-7 细胞对药物的细胞毒性。在相同的热剂量下，光诱导的升温可以将升温与药物治疗的相互作用从干扰转变为协同作用。这是首次通过原位吡咯聚合一锅法合成 PLGA/PPy 纳米复合材料的报道，这种多功能纳米平台被证明是光诱导温和升温和增强化疗的有前途的药物。
