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智能聚(氨基酸)纳米复合材料栓塞联合治疗实体瘤的新方法。

A Simple and Efficient Embolization-Combined Therapy for Solid Tumors by Smart Poly(amino acid)s Nanocomposites.

机构信息

Key Laboratory of Eco-functional Polymer Materials of the Ministry of Education, Key Laboratory of Eco-environmental Polymer Materials of Gansu Province, College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070, China.

Institute of Gansu Medical Science Research, Gansu Provincial Cancer Hospital, Lanzhou 730050, China.

出版信息

ACS Appl Bio Mater. 2022 Feb 21;5(2):661-674. doi: 10.1021/acsabm.1c01106. Epub 2022 Feb 9.

Abstract

Interventional embolization and minimally invasive thermal ablation are common clinical methods for treatment of unresectable solid tumors, but they both have many insurmountable disadvantages. Inspired by pH-responsive drug delivery systems, we report the tumor microenvironment-gelled nanocomposites with poly[(l-glutamic acid--l-tyrosine)--l-threonine--l-cysteine]s (PGTTCs) coating nanoparticles (NPs, Au or FeO) for noninterventional targeted embolization combined with noninvasive thermal ablation therapy of solid tumors by intravenous injection without catheter use. The results of the animal trial in vivo with tumor-bearing mice and rabbits showed superior targeted embolization and therapy and fluorescence/single-photon emission computed tomography/magnetic resonance multimodal imaging effects. Tumors treated with NPs@PGTTCs were shrunken and necrotized within 30 days, the long-term survival rate was more than 80%, and the same effects can be achieved within 15 days when combined with thermal ablation. The method is so simple and efficient for many hard-to-treat tumors within an acidic microenvironment, which is not only a great improvement and innovation in tumor theranostics but also an important development in nanomedicine.

摘要

介入栓塞和微创热消融是治疗不可切除实体瘤的常用临床方法,但它们都有许多难以克服的缺点。受 pH 响应性药物输送系统的启发,我们报告了具有聚(L-谷氨酸-L-酪氨酸)-L-苏氨酸-L-半胱氨酸涂层纳米粒子(Au 或 FeO)的肿瘤微环境凝胶纳米复合材料,可通过静脉注射进行非介入性靶向栓塞,无需使用导管,联合非侵入性热消融治疗实体瘤。在荷瘤小鼠和兔的动物试验中,结果表明具有优异的靶向栓塞和治疗以及荧光/单光子发射计算机断层扫描/磁共振多模态成像效果。用 NPs@PGTTCs 处理的肿瘤在 30 天内缩小和坏死,长期存活率超过 80%,与热消融联合使用时,15 天内即可达到相同效果。对于许多处于酸性微环境中的难以治疗的肿瘤,这种方法既简单又高效,不仅是肿瘤治疗学的重大改进和创新,也是纳米医学的重要发展。

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