Metabolizable pH/H2O2 dual-responsive conductive polymer nanoparticles for safe and precise chemo-photothermal therapy
Metabolizable pH/H2O2 dual-responsive conductive polymer nanoparticles for safe and precise chemo-photothermal therapy
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可代谢 pH/H2O2 双响应导电聚合物纳米粒子，用于安全、精确的化学光热治疗
DOI：
10.1016/j.biomaterials.2021.121115
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发表时间：
2021-09-03
期刊：
影响因子：
14
通讯作者：
Ge, Dongtao
中科院分区：
文献类型：
--
作者：
Liu, Xin;Liu, Yang;Ge, Dongtao
具有高近红外吸收率的导电聚合物在癌症治疗，特别是化学光热治疗的智能纳米药物的设计中引起了相当大的关注。然而，由于导电聚合物的不可降解性，其在体内的长期生物安全性尚不明确，阻碍了其临床应用。本文中，制备了H2 O2触发的可降解导电聚合物，聚丙烯酸（PAA）稳定的聚（吡咯-3-COOH）（PAA@PPyCOOH），以与多柔比星（DOX）形成纳米颗粒，用于安全和精确的化学-光疗。结果表明，PAA@PPyCOOH具有良好的分散性、良好的生物相容性和较高的光热转换效率（56%），是一种理想的光热纳米材料。在进一步负载阿霉素（DOX）后，PAA@PPyCOOH@DOX表现出出色的光热性能，以及在具有酸性和过表达H2 O2微环境的肿瘤中DOX的pH/H2 O2双响应释放，从而产生优异的上级化学光热治疗效果。PAA@PPyCOOH的降解机理可能是吡咯-3-COOH单元与H2 O2的开环反应。更重要的是，纳米颗粒可以被肿瘤中过量的H2 O2特异性降解，并且降解产物被证实通过尿液和粪便排出。体内实验结果表明，光化学热疗对4 T1乳腺癌模型的肿瘤生长有明显的抑制作用，且无明显的毒副作用，具有潜在的临床应用价值。
Conductive polymers with high near-infrared absorbance, have attracted considerable attention in the design of intelligent nanomedicines for cancer therapy, especially chemo-photothermal therapy. However, the unknown long-term biosafety of conductive polymers in vivo due to non-degradability hinders their clinic application. Herein, a H2O2-triggered degradable conductive polymer, polyacrylic acid (PAA) stabilized poly(pyrrole-3-COOH) (PAA@PPyCOOH), is fabricated to form nanoparticles with doxorubicin (DOX) for safe and precise chemo-phototherapy. The PAA@PPyCOOH was found to be an ideal photothermal nano-agent with good dispersity, excellent biocompatibility and high photothermal conversion efficiency (56%). After further loading of doxorubicin (DOX), PAA@PPyCOOH@DOX demonstrates outstanding photothermal performance, as well as pH/H2O2 dual-responsive release of DOX in tumors with an acidic and overexpressed H2O2 microenvironment, resulting in superior chemo-photothermal therapeutic effects. The degradation mechanism of PAA@PPyCOOH is proposed to be the ring-opening reaction between the pyrrole-3-COOH unit and H2O2. More importantly, the nanoparticles can be specifically degraded by excess H2O2 in tumor, and the degradation products were confirmed to be excreted via urine and feces. In vivo therapeutic evaluation of chemo-photothermal therapy reveals tumor growth of 4T1 breast cancer model is drastically inhibited and no apparent side-effect is detected, thus indicating substantial potential in clinic application.