A Targeted Erythrocyte Membrane-Encapsulated Drug-Delivery System with Anti-osteosarcoma and Anti-osteolytic Effects

Chemotherapy is one of the main treatment methods for osteosarcoma. However, conventional chemotherapy lacks targeting properties, and its long-term and extensive use will have serious side effects on patients. For this reason, a multifunctional nanodrug system (V-RZCD) targeting osteosarcoma was developed in this study. V-RZCD consists of two parts: (1) the core (ZCD), wherein calcium ions (Ca²⁺) and zoledronic acid (ZA) form a metal-organic framework for loading doxorubicin (DOX), and (2) the shell (V-R), a vascular endothelial growth factor (VEGF) ligand-modified red blood cell membrane nanovesicle. By targeting the VEGF, V-RZCD can specifically bind to the VEGF receptors that are highly expressed on the surface of osteosarcoma cells. Importantly, compared with free ZA and DOX, V-RZCD not only clearly inhibits the proliferation of osteosarcoma but also significantly inhibits osteolysis induced by osteosarcoma. In summary, V-RZCD represents a new way to treat osteosarcoma.