Functionalization of an Injectable Self-Healing pH-Responsive Hydrogel by Incorporating a Curcumin/Polymerized beta-Cyclodextrin Inclusion Complex for Selective Toxicity to Osteosarcoma

Osteosarcoma is a common malignant bone tumor that tends to occur in adolescents, with surgical resection of the tumor tissue as its standard treatment. After surgery, long-term chemotherapy should be performed to prevent patients from recrudescence. However, conventional chemotherapy drugs impose many serious side effects on patients. It is significant to optimize a chemotherapy drug delivery system. Herein, we present an injectable self-healing hydrogel carrying curcumin with pH-responsive drug release and selective toxicity for osteosarcoma therapy. Amino-gelatin and oxidized starch were synthesized and used as substrates to prepare hydrogels based on imine linkages. Polymerized beta-CD was synthesized to encapsulate curcumin and incorporate it into hydrogels. As a dynamic covalent bond, imine linkages endowed the hydrogel with injectability and self-healing properties. Under acidic conditions, the hydrogel presented a pH-responsive curcumin release property due to instable imine linkages, showing a higher cumulative release of curcumin at pH 6.5 than at pH 7.4. Moreover, hydrogels could continuously release curcumin for more than 28 days, featuring a sudden early release and a slow late release. Interestingly, differentiated from healthy osteoblasts, the hydrogel showed selective cytotoxicity to osteosarcoma cells and could even accelerate the differentiation of osteoblasts owing to the incorporation of curcumin. Briefly speaking, as a drug delivery system, the composite hydrogel can be widely applied for osteosarcoma treatment.