Tumor Noninvasive and Target Embolization Therapy Platform by Intravenous Injection Based on Acidic Microenvironment-Responsive Hyperbranched Poly(amino acid)s

基于酸性微环境响应型超支化聚氨基酸的肿瘤非侵入性靶向栓塞治疗平台(静脉注射)

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Abstract

Transcatheter arterial embolization (TAE) has been widely applied in treatments of unresectable or hypervascular tumors, but the procedure of TAE is complicated possibly brings inherent risks. Here, inspired by pH-responsive drug delivery systems, a new method of noninvasive and target embolization therapy by intravenous injection was developed. This method is based on a type of acidic microenvironment-responsive hyperbranched poly(amino acid) (HPTTG) to avoid using catheterization and real-time image guidance angiography, simplifying the procedure, elevating compliance and general applicability of embolization therapy. The pH value of the sol-to-gel phase transition with decreasing pH of HPTTG was controlled by adjusting the ratio of acidic amino acids in copolymers. The results of the tumor-bearing animal experiment indicate that the HPTTG have an excellent target and embolic ability; they accumulate the most at the tumor site in 8 h postinjection. Blood vessels of the tumors were occluded, and the tumors were inhibited and necrotized in about 20 days. Therefore, it is expected that HPTTG not only can be used as novel embolic materials for efficient noninvasive embolization therapy of many solid tumors but also can be used as a multifunctional platform for combined theranostics, for example, combination with controlled release, thermal ablation, multimodal imaging, synergistic therapy, etc.

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