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Nano Research

Article Title

Strong dual-crosslinked hydrogels for ultrasound-triggered drug delivery

Authors

Wenxu Sun, Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, and Department of Physics, Nanjing University, Nanjing 210093, China
Heting Jiang, Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, and Department of Physics, Nanjing University, Nanjing 210093, China
Xin Wu, Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, and Department of Physics, Nanjing University, Nanjing 210093, China
Zhengyu Xu, Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, and Department of Physics, Nanjing University, Nanjing 210093, China
Chen Yao, Department of Sports Medicine and Adult Reconstructive surgery, Drum Tower Hospital; Medical School, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing 210008, China Joint Research Center for Bone and Joint Disease, Model Animal Research Center (MARC), School of Chemistry and Chemical Engineering, and State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing 210093, China
Juan Wang, Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, and Department of Physics, Nanjing University, Nanjing 210093, China
Meng Qin, Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, and Department of Physics, Nanjing University, Nanjing 210093, China
Qing Jiang, Department of Sports Medicine and Adult Reconstructive surgery, Drum Tower Hospital; Medical School, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing 210008, China Joint Research Center for Bone and Joint Disease, Model Animal Research Center (MARC), School of Chemistry and Chemical Engineering, and State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing 210093, China
Wei Wang, Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, and Department of Physics, Nanjing University, Nanjing 210093, China
Dongquan Shi, Department of Sports Medicine and Adult Reconstructive surgery, Drum Tower Hospital; Medical School, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing 210008, China Joint Research Center for Bone and Joint Disease, Model Animal Research Center (MARC), School of Chemistry and Chemical Engineering, and State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing 210093, China
Yi Cao, Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, and Department of Physics, Nanjing University, Nanjing 210093, China

Keywords

hydrogel, dynamic covalent bond, mechanical force, drug release

Abstract

Hydrogels that can respond to dynamic forces either from endogenous biological activities or from external mechanical stimuli show great promise as novel drug delivery systems (DDS). However, it remains challenging to engineer hydrogels that specifically respond to externally applied mechanical forces with minimal basal drug leakage under normal stressful physiological conditions. Here we present an ultrasound responsive hydrogel-based DDS with special dual-crosslinked nanoscale network architecture. The covalent crosslinks endow the hydrogel high mechanical stability and greatly suppress deformation-triggered drug release. Meanwhile, the dynamic covalent boronate ester linkages between hydrogel backbone and the anti-inflammation compound, tannic acid (TA), allow effective ultrasound-triggered pulsatile release of TA. As such, the hydrogel shows distinct drug release profiles under compression and ultrasound. A proof-of-principle demonstration of the suppression of inflammation activation of macrophage upon ultrasound-triggered release of TA was also illustrated. We anticipate that this novel hydrogel-based drug delivery system can be used for the treatment of inflammatory diseases on load-bearing tissues, such as muscle and cartilage.

Graphical Abstract

Publisher

Tsinghua University Press

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