A pro-nanodrug combinational strategy for efficient cervical cancer therapy with intrinsic tumor microenvironment (TME)-responsive elements and low side effects is highly desired. Here, a pro-nanodrug complexes with GSH and NIR responsive manner is reported to boost gamabufotalin induced chemo-photothermal therapy with the assistance of reprogrammed TME by indomethacin. In addition, hybrid cell membrane was used to endow nanocomplexes with the prolonging circulation time and high accumulation of drug at tumor tissue. Indomethacin activated by the high level GSH can attenuate tumor inflammation microenvironment triggered by PTT and sensitize tumor cells to gamabufotalin through inhibiting PGE2 secretion. The released low-dose gamabufotalin with low side effects can efficiently kill tumor cells by ROS production and COX-2 low expression. In vitro and in vivo assays demonstrated that strong anti-tumor activity of nanocomplexes in tumor-bearing mice through chemo-photothermal therapy, which was reflected by the eradication of cervical tumor and significant extension of survival time of mice.

非常需要一种具有内在肿瘤微环境（TME）响应元件和低副作用的有效宫颈癌治疗的前纳米药物组合策略。在这里，据报道具有 GSH 和 NIR 响应方式的前纳米药物复合物可在吲哚美辛重新编程的 TME 的帮助下促进 gamabufotalin 诱导的化学光热疗法。此外，混合细胞膜用于赋予纳米复合物延长循环时间和药物在肿瘤组织中的高积累。高水平 GSH 激活的吲哚美辛可以减弱 PTT 触发的肿瘤炎症微环境，并通过抑制 PGE2 分泌使肿瘤细胞对 gamabufotalin 敏感。释放的低剂量加马布福他林通过产生 ROS 和 COX-2 低表达，可以有效杀死肿瘤细胞。