Thermo‐Triggered In Situ Chitosan‐Based Gelation System for Repeated and Enhanced Sonodynamic Therapy Post a Single Injection

• Published in: Advanced healthcare materials 2021-02, Vol.10 (3), p.e2001208-n/a
• Main Authors: She, Jialin, Zhou, Xuanfang, Zhang, Yaojia, Zhang, Rui, Li, Quguang, Zhu, Wenju, Meng, Zhouqi, Liu, Zhuang
• Format: Article
• Language: English
• Subjects: Body temperature; Catalase; Chitosan; Glycerol; Humans; Hydrogels; Hydrogen peroxide; hypoxia relief; in situ gelation; Injection; long‐term retention; Neoplasms - drug therapy; Oxygen; Precursors; Reactive Oxygen Species; Robustness; Side effects; Sol-gel processes; Solid tumors; sonodynamic therapy; thermo‐triggered therapeutics; Tumors; Ultrasonic processing; Ultrasonic Therapy; Ultrasonic Waves
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.202001208

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. A hybrid thermo‐triggered in situ hydrogel system is designed to realize the long‐term local retention of therapeutic agents to reinforce the gel structure in tumors and persistent tumorous hypoxia relief. For mice with a single‐dose injection of precursor solution and multiple rounds of ultrasonic treatments, the repeated SDT could offer the robust treatment effects to eradicate tumors.