Co-delivery of Zn ions and resveratrol via bioactive glass-integrated injectable microspheres for postoperative regeneration of bone tumor defects

Abstract

Postoperative bone regeneration repair for primary or metastatic bone tumors is often impeded by the adverse effects of chemotherapy treatment. As a low-toxicity therapeutic ion, the efficacy of Zn ions in promoting anti-tumor and bone regeneration outcomes has been demonstrated. However, the potential benefits are limited due to inadequate zinc intake in malignant cells and its anti-tumor mechanism remain unclear. Overcoming these difficulties, we report a new strategy for improving the delivery of Zn ions and antitumor drug by fabricating chitosan (CS) cryogel microspheres to synchronize the loading of resveratrol (Res) and Zn-BG. The Zn ions released from Zn-BG were combined with Res, then transported and enriched intracellularly, inducing apoptosis of tumor cells via multiple pathways. Moreover, the Zn-BG@Res-CS cryogel microspheres exhibited antibacterial and osteogenic effects. In particular, we found that this delivery system significantly inhibited tumor development and metastasis in vivo. Our founding suggests that the combination of Zn ions with Res could enhance cell uptake of Zn ions then induce apoptosis of tumor cells selectively. This study indicates that the combination chemotherapy and biomaterial construction could be a potential therapeutic approach for postoperative regeneration of bone tumor defects.