pH/ultrasound dual-responsive gas generator for ultrasound imaging-guided therapeutic inertial cavitation and sonodynamic therapy

【作者】 Qianhua Feng, Wanxia Zhang, Xuemei Yang, Yuzhen Li, Yongwei Hao, Hongling Zhang, Lin Hou, Zhenzhong Zhang

【期刊名】Advanced Healthcare Materials

【影响因子】 2018年:6.270

【作者单位】 School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, China

【年，卷(期)：页码】2018, 7: 1700957

【关键词】 mesoporous calcium carbonate nanoparticles; ultrasound imaging; inertial cavitation; sonodynamic therapy

【摘要】Herein, we reported a pH/ultrasound dual-responsive gas generator, which was based on mesoporous calcium carbonate nanoparticles (MCC NPs) by loading sonosensitizer (hematoporphyrin monomethyl ether, HMME) and modifying surface hyaluronic acid (HA). After pinpointing tumor regions with prominent targeting efficiency, HMME/MCC-HA decomposed instantaneously under theco-triggering of tumoral inherentacidic condition and ultrasound(US) irradiation, concurrently accompanying with CO₂ generation and HMME release with spatial/temporal resolution. Afterwards, the CO₂bubbling and bursting effect under US stimulus resulted in cavitation-mediated irreversible cell necrosis, as well asthe blood vessel destruction to further occlude the blood supply, providing a “bystander effect”. Meanwhile, reactive oxygen species (ROS) generated from HMME could target the apoptotic pathways for effective sonodynamic therapy. Thus, the combination of apoptosis/necrosis with multi-mechanisms consequently resulted in a remarkable anti-tumor therapeutic efficacy, simultaneously minimizing the side effects on major organs. Moreover, the echogenic property of CO₂ made the nanoplatform as a powerful ultrasound contrast agent to identify cancerous lesions. Based on the above findings, we utilized such all-in-one drug delivery platform of HMME/MCC-HA to provide the US imaging guidance for therapeutic inertial cavitn and sonodynamic therapy simultaneously, which highlighted possibilities of advancing cancer theranostics in biomedical fields.

【全文链接】

https://onlinelibrary_wiley.gg363.site/doi/abs/10.1002/adhm.201700957