肿瘤靶向负载IR780的棉酚-Fe(Ⅲ)-绿茶多酚(EGCG) 无限配位聚合物纳米粒及其肿瘤光热/协同化疗

In order to solve the problems of strong photothermal therapy, weak chemotherapy of photothermal/ chemotherapy and low efficiency and short - term effect of synergistic chemotherapy. In this project, a novel strategy of tumor photothermal / synergistic chemotherapy ( tumor photothermal first and then synergistic chemotherapy )under the montoring of magnetic resonance and fluorescence imaging is proposed. Thus we design a highly efficient, multi-functional nanosystem with the integrated characteristics of tumor targeting, tumor photothermal / synergistic chemotherapy and imaging monitoring. Nature products of Gossypol, Epigallocatechin gallate (EGCG) are coordinated with Fe（Ⅲ) and bottle green Gossypol-Fe (Ⅲ)-EGCG infinite coordination polymer nanoparticles are formatted, the nanosystem is finally obtained after IR780 loaded with Gossypol-Fe (Ⅲ)-EGCG nanoparticles and hyaluronic acid surface modification. Their chemical structure is confirmed by IR spectra, magnetic resonance and XPS spectra. Their tumor targeting effect and drug metabolism characters are studied by fluorescent spectra, magnetic resonance and fluorescence imaging in vivo, their tumor photothermal / synergistic chemotherapy results are studied by in vitro and in vivo experiments. This nanosystem has the adjustable constitutes with the characteristics of tumor photothermal / synergistic chemotherapy and imaging monitoring, maximize using efficiency of constituted materials, in which Gossypol and EGCG can be either used for carrier materials or the constitutes of synergistic chemotherapy; and they are also used for tumor photothermal therapy after bottle green Gossypol-Fe (Ⅲ)-EGCG infinite coordination polymer nanoparticles formatted. IR 780 can be both used for enhancement photothermal effect of the infinite coordination polymer nanoparticles and used drug metabolism character with fluorescence imaging. This kind of nanosystem has the simple constitute and powerful multi-functions, indicating its higher comprehensive therapeutic effect for tumor treatment.

为克服光热疗/化疗中热疗强、化疗弱和联合化疗起效慢、短期疗效差的不足，本项目提出了先光热疗、再协同化疗的抗肿瘤新策略。为此设计了高效、多功能集肿瘤靶向、光热治疗、协同化疗和影像监控等特性于一体的纳米系统，将天然抗肿瘤药棉酚、绿茶多酚(EGCG)与Fe（Ⅲ)配位形成深绿色无限配位聚合物纳米粒并负载荧光染料IR780，再表面修饰透明质酸形成纳米系统。用红外光谱、XPS和核磁共振等确定其化学构成；核磁和活体荧光成像等研究其肿瘤靶向和药物代谢性质，体内外实验研究其肿瘤综合治疗效果。该系统组分比例可调、兼有强光热疗和强多药协同化疗功能并可影像监控、有极高的组分利用率和药物负载量且一物多用。棉酚、EGCG既是纳米粒载体和协同化疗成分、形成的深色配合物又可用于光热疗。IR780既可增强聚合物的光热效果，还用于荧光监控药物释放与分布。该系统综合疗效高、功能强大、结构简单，将为肿瘤的综合治疗开辟新途径。

为克服光热疗/化疗中热疗强、化疗弱和联合化疗起效慢、短期疗效差的不足，本项目提出了先光热疗、再协同化疗的两阶段双协同抗肿瘤新策略。为此设计了高效、多功能集肿瘤靶向、光热治疗、协同化疗和影像监控等特性于一体的纳米系统，将棉酚和绿茶多酚与Fe3+配位形成无限配位聚合物，掺杂1.3%光热剂IR780，再以包封具有肿瘤靶向能力的透明质酸（HA）为外壳，制备负载IR780的透明质酸包裹棉酚-Fe(III)-儿茶酚无限配位聚合物纳米颗粒（HA@IRGFE ICP NPs），用红外光谱、XPS和核磁共振等确定其化学构成；核磁和活体荧光成像等研究其肿瘤靶向和药物代谢性质，体内外实验研究其肿瘤综合治疗效果。体外实验证明HA@IRGFE ICP NPs先释放IR780和ICPs光热/化疗协同治疗，然后ICPs中两种药物释放联合化疗，达到了两阶段双协同肿瘤治疗效果。动物实验表明该方法的肿瘤抑制率高达98.7%，60天后肿瘤的复发率仅为12.5%。实现了肿瘤的高效光热和双药ICPs协同治疗，该系统全部由天然产物组成，对正常组织毒副作用极低，该系统组分比例可调、兼有强光热疗和强多药协同化疗功能并可影像监控、有极高的组分利用率和药物负载量且一物多用。 棉酚、EGCG既是纳米粒载体和协同化疗成分、形成的深色配合物又可用于光热疗。IR780既可增强聚合物的光热效果，还用于荧光监控药物释放与分布。该系统综合疗效高、功能强大、结构简单，将为肿瘤的综合治疗开辟新途径。