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Thermo‐Triggered In Situ Chitosan‐Based Gelation System for Repeated and Enhanced Sonodynamic Therapy Post a Single Injection
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2020-11-25 , DOI: 10.1002/adhm.202001208
Jialin She 1 , Xuanfang Zhou 1 , Yaojia Zhang 1 , Rui Zhang 1 , Quguang Li 1 , Wenju Zhu 1 , Zhouqi Meng 1 , Zhuang Liu 1
Affiliation  

Sonodynamic therapy (SDT) by utilizing ultrasonic waves triggers the generation of reactive oxygen species (ROS) with the help of sonosensitizers to destruct deep‐seated tumors has attracted great attention. However, the efficacy of SDT may not be robust enough due to the insufficient oxygen supply within solid tumors. Additionally, repeated injections and treatments, which are often required to achieve the optimal therapeutic responses, may cause additional side effects and patient incompliance. Herein, a thermo‐triggered in situ hydrogel system is developed in which catalase (CAT) conjugated with sonosensitizer meso‐tetra (4‐carboxyphenyl) porphine (TCPP) is mixed into chitosan (CS) and beta‐glycerol phosphate disodium (GP) to form the precursor solution. After injection of the precursor solution into tumors, the in situ sol–gel transformation will occur as triggered by the body temperature, resulting in the localized tumor retention of TCPP‐CAT. The locally restrained TCPP‐CAT not only produces ROS under ultrasonic treatment, but also sustainably reverses the oxygen‐deficient status in solid tumors by triggering the O2 generation from the decomposition of endogenous H2O2, further promoting the efficacy of SDT. As a result, the repeated SDT after a single dose injection of such a hydrogel can offer robust treatment effects to effectively eradicate tumors.

中文翻译:

单次注射后基于热触发的原位壳聚糖凝胶化系统可进行重复和增强的声动力学治疗

利用超声波的声波动力疗法(SDT)借助声敏剂破坏深层肿瘤触发了活性氧(ROS)的产生,引起了广泛的关注。然而,由于实体瘤内氧气供应不足,SDT的功效可能不够强健。另外,经常需要重复注射和治疗以达到最佳治疗效果,这可能会导致其他副作用和患者不适应症。本文开发了一种热触发原位水凝胶系统,其中将与声敏剂中四(4-羧基苯基)卟啉(TCPP)共轭的过氧化氢酶(CAT)混合到壳聚糖(CS)和β-甘油磷酸二钠(GP)中,形成前体溶液。将前体溶液注入肿瘤后,体温触发将发生原位溶胶-凝胶转变,从而导致TCPP-CAT的局部肿瘤保留。受局部约束的TCPP-CAT不仅在超声处理下产生ROS,而且通过触发O来持续逆转实体瘤中的缺氧状态内源性H 2 O 2分解产生2代,进一步促进了SDT的功效。结果,在单剂量注射这样的水凝胶之后重复的SDT可以提供强有力的治疗效果以有效根除肿瘤。
更新日期:2021-02-03
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