Light-responsive Micelles Loaded With Doxorubicin For Osteosarcoma Therapy

Objective: To achieve the goal of photosensitive targeted therapy to enhance the therapeutic effect of osteosarcoma,light-responsive micelles loaded with Doxorubicin（Dox）were constructed.And we further explore the therapeutic effect of micelles against osteosarcoma.Methods:（1）Conjugated polymer Poly-Dox was prepared from4’-Hydroxy-3’-methoxyacetophenone,and drug-loaded micellar polymer Poly-Dox-Micelles（Poly-Dox-M）was investigated by solvent dialysis.The characteristics of Poly-Dox-M were characterized by TEM,and the light-responsiveness drug release behavior of the nano-micelle was investigated.（2）K7M2wt cells were used as a cellular experimental model to investigate the cell uptake and cytotoxicity of the micellar polymer after different light exposure.（3）The mouse model of osteosarcoma was established,the anti-tumor effect of the light-responsiveness nano-micelle in vivo was investigated,and its biological safety was evaluated.Results:（1）The doxorubicin conjugated polymer Poly-Dox synthesized in this study can self-assemble to form polymeric micelles in water.TEM results show that the micelle was uniform in size and good in dispersion.In addition,Poly-Dox-M can be depolymerized rapidly after UV irradiation,which has extremely sensitive photoresponsive drug release properties.（2）The results of the cellular uptake study showed that the uptake ability of osteosarcoma cells to Poly-Dox-M was significantly enhanced after UV irradiation.Cytotoxicity experiments show that Poly-Dox-M led to more dramatic cytotoxicity under irradiation.（3）The results of in vitro cell experiments showed that the uptake of Poly-Dox-M by osteosarcoma cells was weak,but it was significantly enhanced by light exposure.The results of the cytotoxicity assay showed that the cytotoxicity of Poly-Dox-M was less than that of free Dox,but its cytotoxicity was significantly enhanced after light exposure.Conclusion: In this study,doxorubicin conjugated polymer Poly-Dox with light-responsiveness was synthesized,which can self-assemble to form polymeric micelles（Poly-Dox-M）in water.As an inert structure,the polyethylene glycol（PEG）on the surface of micelles can shield the adsorption of protein and avoid becoming a protein crown in blood,improving the tumor targeting of drugs and reducing the systemic toxicity of Dox.Besides,after ultraviolet irradiation,the amide bond connecting Dox with PEG can be broken,which induced the responsive detachment of PEG and enhanced cellular uptake of Dox.Notably,the results of immunohistochemistry in vivo showed that Poly-Dox-M had no significant damage to normal organs.Meanwhile,they showed efficient tumor-suppressive effects.This nano-delivery system with the light-responsive feature might hold great promises for the targeted therapy for osteosarcoma.