Alendronate-modified polydopamine-coated paclitaxel nanoparticles for osteosarcoma-targeted therapy

Abstract

To improve the treatment effects of chemotherapy on osteosarcoma, we synthesized novel nanoparticles (NPs) coated with polydopamine (PDA) and grafted by alendronate (ALN) as ligand. Dopamine polymerization is a versatile modification technique that is not limited by the lack of functional groups on the compound surfaces and does not alter the chemical properties. The PDA-NPs were successfully conjugated with a typical surface modifier, which had a specific affinity for osteosarcoma cells: alendronate (ALN), as a targeting paclitaxel (PTX) carrier. We fabricated the NPs with average particle size of 255.12 ± 1.560 nm, zeta potential of −17.4 ± 3.27 and PDI value of 0.193 ± 0.026. The nanoparticles were stable in physiological saline, isotonic glucose (5% glucose), phosphate buffered saline (PBS, PH 7.4) and plasma and displayed sustained drug release behavior. Furthermore, the targeting nanoparticles exhibited a stronger in vitro cytotoxicity against K7M2 wt osteosarcoma cells compared to free nanoparticles. In vivo study demonstrated that the targeting NPs could accumulate to a greater extent within the tumor than nontargeted nanoparticles, which prominently decreased the side effects of PTX and achieved better therapeutic efficacy than PTX injection (8 mg/kg, i.v.) (82.51% versus 66.63%). Therefore, the PTX-PDA-ALN-NPs represent a potential drug for osteosarcoma-targeted therapy.