Local delivery of sunitinib and Ce6 via redox-responsive zwitterionic hydrogels effectively prevents osteosarcoma recurrence

Abstract

Surgery combined with adjuvant or neoadjuvant chemotherapy is still the standard treatment for osteosarcoma. However, the high risk of tumor recurrence and side effects of chemotherapy usually lead to high mortality for cancer patients. Herein, the multi-targeted receptor tyrosine kinase (RTK) inhibitor sunitinib (Sun) and photodynamic therapy (PDT) drug chlorin e6 (Ce6) were locally delivered to the postoperative tumor site via a zwitterionic hydrogel. This hydrogel exhibited excellent biocompatibility and redox responsiveness. In vitro study demonstrated that Sun/Ce6@Gel induced 143B human osteosarcoma cell apoptosis via downregulating the expression of Bcl-2 and upregulating the expression levels of Bax and caspase-3. Similarly, the in vivo study showed that Sun/Ce6@Gel provided sustained drug release under redox conditions, and then synergistically induced tumor apoptosis to prevent tumor recurrence without systemic toxicity. Therefore, local implantation of Sun/Ce6@Gel may be a promising topical therapeutic method for prevention of the recurrence of osteosarcoma after surgery.