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

Abstract

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 β-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.

A Multifunctional, Tough, Stretchable, and Transparent Curcumin Hydrogel with Potent Antimicrobial, Antioxidative, Anti-inflammatory, and Angiogenesis Capabilities for Diabetic Wound Healing

“…The Cur release of PCSA hydrogels was evaluated by the reported method with some modifications. 34 In brief, the PCSA hydrogels (0.2 g) were added to 50 mL centrifuge tubes containing PBS (30 mL). All of the samples were shaken on a magnetic stirrer at 37 °C at a speed of 150 rpm.…”

Microenvironment-targeted strategy steers advanced bone regeneration

“…The acidic microenvironment further decreases pH, promoting increased bone resorption. Yuan et al designed a composite hydrogel with selective toxicity to osteosarcoma tissues [ 150 ]. The loaded curcumin can be released in a pH-responsive manner at acidic osteosarcoma sites through the breakage of subamine bonds in the hydrogel, achieving selective toxicity to osteosarcoma cells.…”

Self-Healing Hydrogels: From Synthesis to Multiple Applications

“…In recent years, self-healing performance has been introduced into polymer hydrogel networks to enhance the durability and service life. Self-healing hydrogels can be applied in adjuvant cancer therapy, drug carriers, biological tissue engineering, wound dressings, actuators, human sensors, robotics, 3D printing, contact lenses, etc. − The self-healing processes can be segmented into spontaneous and nonspontaneous processes. In some systems, the self-healing process can take place spontaneously.…”