Folic acid-targeted macrophage membrane-coated carbon quantum dot nanoplatform for dual drug and gene delivery in metastatic osteosarcoma therapy

Osteosarcoma is the most common primary bone tumor with a high metastatic rate. Despite the improvement in patient prognosis with conventional therapeutics, enhancing the survival of patients with metastatic disease remains a challenge. Zoledronic acid (ZOL) stimulates apoptosis in cancer cells and is considered a promising drug for osteosarcoma therapy. Moreover, depletion of Inhibin Subunit Beta A (INHBA), a member of the transforming growth factor superfamily, can suppress osteosarcoma cell proliferation and invasion. Regarding the restricted potential of monotherapy, combination therapies, such as small interfering RNA (siRNA) and chemotherapy, are ideal strategies. However, off-target effects and adverse impacts lead to unsatisfactory clinical efficacy of these drugs. To address this challenge, we designed a folic acid-modified macrophage membrane coated with a carbon quantum dot (CQD) nanoplatform for the co-delivery of ZOL and siINHBA (ZOL-siINHBA@CQD@RM-FA). The anticancer activity of this nanotherapeutic agent was examined in vitro and in vivo. ZOL-siINHBA@CQD@RM-FA was approximately 200.7 nm in size, had a negative charge, excellent pH responsiveness, desirable biocompatibility, and high cellular uptake. This nanosystem achieved favorable co-delivery of ZOL/siINHBA and impaired osteosarcoma proliferation and invasion in vitro. Notably, intravenous administration facilitated tumor growth regression and inhibited lung metastasis without systemic toxicity. Accordingly, this nanotherapy could be considered an effective treatment for osteosarcoma, and this nanodelivery system shows potential for combined therapy by co-delivering genes and chemotherapy drugs.