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

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.