Injectable Self-Healing Cellulose Hydrogel Based on Host-Guest Interaction and Acylhydrazone Bond for Sustained Cancer Therapy

Abstract

Tumor local chemotherapy employing injectable hydrogels reservoirs is a promising platform to achieve precise drug administration. However, balanced injectability, pH-responsiveness and long-term hydrolysis resistance of self-healing hydrogels remains an appealing challenge. Herein, a modular preassembly strategy combining host-guest interactions with dynamic acylhydrazone bonds, was exploited to fabricate injectable cellulose-based hydrogels dressed with outstanding self-healing property, pH-responsiveness and hydrolytic degradation resistance. Attributed to the host-guest interaction between β-cyclodextrin and 1-adamantane, the hydrogels exhibited excellent injectability, self-healing property (healing efficiency of 97.5 %) and rapid recovery ( 30 days) and pH-responsive behavior, endowing the hydrogels with precisely spatio-temporal drug release administration. When used for osteosarcoma therapy, the average tumor weight (25 mg) treated with doxorubicin (DOX) loaded hydrogel was much smaller than DOX group (161 mg) and control group (553mg), demonstrating the DOX-loaded hydrogels achieved high inhibition efficacy against tumor recurrence without obvious long-term toxicity. Funding Information: This work was supported by the Major International (Regional) Joint Research Project of National Natural Science Foundation of China (21620102004), the National Natural Science Foundation of China (51973166), the Key Research and Development Program of HubeiProvince (2020BCA079), and Hubei Province Scientific and Technical Innovation Key Project (No. 2019ACA136). Declaration of Interests: The authors declare no known conflict of interest. Ethics Approval Statement: All Animal experiments were approved by the Institutional Animal Care and Use Committee (IACUC) of Wuhan University (No. WP2020-08082).