Engineering PDA-coated CM-CS nanoparticles for photothermo-chemotherapy of osteosarcoma and bone regeneration

Abstract

After an osteosarcoma excision, recurrence and bone defects are significant challenges for clinicians. Combination therapy based on a nanoparticle-based drug delivery system shows great promise in osteosarcoma therapy. In this study, we designed a multifunctional chitosan (CS) nanoparticle, which combined photothermal therapy (PTT) with chemotherapy to synergistically enhance osteosarcoma therapy and bone repair. Curcumin (CM) loaded CS nanoparticles were prepared through ionotropic gelation method and were further functionalized with polydopamine (PDA) coating to form CS-CM-PDA nanoparticles (CCPNPs). The CCPNPs displayed pH- and near-infrared (NIR)- responsive CM release behavior. In vitro anti-cancer results indicated that CCPNPs possessed a long-term stable anti-cancer effect compared to pure CM. The presence of the NIR irradiation combined with CCPNPs resulted in a dramatic decrease in MG-63 osteosarcoma cell viability in 10 min compared with the pure CCPNPs at the concentration of 500 μg/mL. Meanwhile, in vitro study demonstrated that CCPNPs induced MG-63 cell apoptosis via downregulating the expression of Bcl-2 and upregulating the expression levels of Bax and Caspase-3. Besides, CCPNPs could positively induce the proliferation of MC3T3-E1 osteoblast cells in vitro. These results suggested that CCPNPs with bifunctional osteosarcoma therapy and bone repair may be an excellent candidate for local cancer therapy and bone regeneration.