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用于超声成像引导下治疗性惯性空化和超声动力治疗的pH/超声双响应气体发生器

pH/Ultrasound Dual-Responsive Gas Generator for Ultrasound Imaging-Guided Therapeutic Inertial Cavitation and Sonodynamic Therapy.

作者信息

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

机构信息

School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, P. R. China.

Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Zhengzhou, 450001, P. R. China.

出版信息

Adv Healthc Mater. 2018 Mar;7(5). doi: 10.1002/adhm.201700957. Epub 2017 Nov 15.

Abstract

Herein, a pH/ultrasound dual-responsive gas generator is reported, which is based on mesoporous calcium carbonate (MCC) nanoparticles by loading sonosensitizer (hematoporphyrin monomethyl ether (HMME)) and modifying surface hyaluronic acid (HA). After pinpointing tumor regions with prominent targeting efficiency, HMME/MCC-HA decomposes instantaneously under the cotriggering of tumoral inherent acidic condition and ultrasound (US) irradiation, concurrently accompanying with CO generation and HMME release with spatial/temporal resolution. Afterward, the CO bubbling and bursting effect under US stimulus results in cavitation-mediated irreversible cell necrosis, as well as the blood vessel destruction to further occlude the blood supply, providing a "bystander effect." Meanwhile, reactive oxygen species generated from HMME can target the apoptotic pathways for effective sonodynamic therapy. Thus, the combination of apoptosis/necrosis with multimechanisms consequently results in a remarkable antitumor therapeutic efficacy, simultaneously minimizing the side effects on major organs. Moreover, the echogenic property of CO make the nanoplatform as a powerful ultrasound contrast agent to identify cancerous lesions. Based on the above findings, such all-in-one drug delivery platform of HMME/MCC-HA is utilized to provide the US imaging guidance for therapeutic inertial cavitation and sonodynamic therapy simultaneously, which highlights possibilities of advancing cancer theranostics in biomedical fields.

摘要

在此,报道了一种pH/超声双响应气体发生器,它基于介孔碳酸钙(MCC)纳米颗粒,通过负载声敏剂(血卟啉单甲醚(HMME))和修饰表面透明质酸(HA)制备而成。在以显著的靶向效率精准定位肿瘤区域后,HMME/MCC-HA在肿瘤固有酸性条件和超声(US)照射的共同触发下瞬间分解,同时伴随CO生成和HMME以时空分辨率释放。随后,在US刺激下的CO气泡形成和破裂效应导致空化介导的不可逆细胞坏死,以及血管破坏以进一步阻断血液供应,从而产生“旁观者效应”。同时,HMME产生的活性氧可靶向凋亡途径以进行有效的声动力治疗。因此,凋亡/坏死与多种机制的结合产生了显著的抗肿瘤治疗效果,同时将对主要器官的副作用降至最低。此外,CO的回声特性使该纳米平台成为一种强大的超声造影剂,可用于识别癌性病变。基于上述发现,这种HMME/MCC-HA一体化药物递送平台可同时为治疗性惯性空化和声动力治疗提供US成像引导,这凸显了在生物医学领域推进癌症诊疗一体化的可能性。

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