Local delivery of sunitinib and Ce6viaredox-responsive zwitterionic hydrogels effectively prevents osteosarcoma recurrence

摘要

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 siteviaa zwitterionic hydrogel. This hydrogel exhibited excellent biocompatibility and redox responsiveness.In vitrostudy demonstrated that Sun/Ce6@Gel induced 143B human osteosarcoma cell apoptosisviadownregulating the expression of Bcl-2 and upregulating the expression levels of Bax and caspase-3. Similarly, thein vivostudy 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.