Xu Zihan, He Xiujing, Gui Yu, Tang Lingkai, Zhao Yuxin, Song Linlin, Xu Tianyue, Chen Meixu, Zhao Yujie, Du Peixin, Wang Xin, Chen Siyi, Luo Yong, Luo Feng, Meng Huan, Hu Jianping, Zhuo Wei, Jing Jing, Shi Hubing
Institute of Breast Health Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan, China.
Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Nat Commun. 2025 Apr 3;16(1):3194. doi: 10.1038/s41467-025-58354-9.
Malignant pleural effusion (MPE), persistently generated by thorax tumor cells at the advanced stage, remains a major challenge for cancer therapy. Herein, we develop an ultra-sensitive piezoelectric nano-system by doping ytterbium in metal-organic framework (OP@LPYU), which can be triggered by physiological intrapleural pressure during breath. Under the gently alterative pressure, the piezoelectric nanoparticles with notable peroxidase-like activity effectively produce a burst of reactive oxygen species and induce immunogenic cell death by catalysis of carried ozone as well as peroxide in interstitial fluid. A clear and sustained biodistribution is observed in thorax effusion and tumors upon intrapleural administration of particle. Remarkably, due to the abundant substrates in oxygen-rich environment of pleural cavity, OP@LPYU particle provides a potent reduction of MPE volume and durable inhibition of tumor growth in thorax. Our work not only develops a bio-responsive piezoelectric nano-system, but also provides a strategy for persistent suppression of MPE in clinics.
恶性胸腔积液（MPE）是由晚期胸部肿瘤细胞持续产生的，仍然是癌症治疗的一项重大挑战。在此，我们通过在金属有机框架中掺杂镱（OP@LPYU）开发了一种超灵敏的压电纳米系统，其可在呼吸过程中由生理胸腔内压触发。在轻微交替压力下，具有显著过氧化物酶样活性的压电纳米颗粒通过催化间质液中携带的臭氧和过氧化物有效产生大量活性氧并诱导免疫原性细胞死亡。在胸腔内给予颗粒后，在胸腔积液和肿瘤中观察到清晰且持续的生物分布。值得注意的是，由于胸腔富含氧气环境中的丰富底物，OP@LPYU颗粒有效减少了MPE体积，并持久抑制了胸部肿瘤的生长。我们的工作不仅开发了一种生物响应性压电纳米系统，还为临床上持续抑制MPE提供了一种策略。
