Self-stabilized Hyaluronate Nanogel For Intracellular Co-delivery Of Doxorubicin And Cisplatin To Osteosarcoma

Objective: Osteosarcoma is one of the most common and serious malignancies with rapid deterioration speed and low survival rate in children and teenagers,due to the low efficacy and high risk of conventional small molecule therapeutics in the clinical treatment.Hence,the drug delivery systems based on nanotechnology may have great potential to break through these barriers,especially for the self-stabilized co-delivery system which reveal prolong circulation time,higher tumor accumulation ability,and reduced side effects.Methods: The K7 murine osteosarcoma cell line was utilized in this work and 21 female BALB/C mice with the average weight of 20 g were used to evaluate the in vivo antitumor efficacy.After the successful preparation of drug loaded nanogel,we verify its potential on tumor inhibition by a series of tests including DLS,drug release,cytotoxicity assays,pharmacokinetics test,drug’s distribution,tumor inhibition,survival rate,and immunofluorescence assay etc.Results: Comparing to the free drug,the drug loaded nanogel revealed better performance on controlling drug release and biocompatibility.The tumor inhibition rate of the drug loaded nanogel treated group(89.1±3.5%)was significantly higher compare to that of the free drug treated group 62.1±5.0%(P <0.01).Conclusion: 1,By the in suit crosslinking,the drug loaded self-stabilized hyaluronate nanogel displayed stronger stability.2,This drug co-delivery system has the ability of controlling the drug’s delivery in vitro and in vivo.3,This tumor-targeting drug delivery could effectively enhance the antitumor efficiency.