Light Response Nano-systems Containing Platinum Used For Tumor Diagnosing And Treatment

Traditional drug carriers already far can't meet the demand of the cancer therapies' development.The polymer micelle,one of the most efficient drug delivery systems,has gained great attention at present time.Polymer micelles have many potential advantages,such as improving the bioavailability,solubility and the blood circulation time of most hydrophobic durgs through enhanced permeability and retention(EPR)effect.Cisplatin,which has been wildly used in clinical cancer therapy,has great performance in tumor treatment.However,the limitations of the Cisplatin utility have still existed on account of its high toxicity,drug resistance and side effects.The active platimum(II)can be reduced from photosensitive Pt(IV)prodrugs under light irradiation,and a variety of light-regulated reductions can be achieved by adjusting the Pt(IV)' ligands.However,the wavelength of the light-responsive polymer is substantially fixed at present,and the function of the applied light-responsive monomer was relatively simple.Meanwhile,the product of the light-sensitive compound after photostimulation has a considerable systemic toxicity.Previously,the research of photosensitive Pt(IV)mainly focused on its application as anti-tumor prodrug in the control release system,but there are still some problems have not been solved.According to the existing work in our group,photosensitive Pt(IV)was used as a photo-stimulation response unit to participate in construction of photosensitive main chain segmented copolymers have a wide range of applications for controlled release.Therefore,it is significant to design and synthesize new multifunctional materials by introducing other functional molecules,on the basis of containing the photosensitive platinum in main chain.Under the premise of satisfying the anti-tumor effect,we hope to give the material more functions.Therefore,we introduced the aggregation-induced emission(AIE)compounds and photosensitive Pt(IV)into the backbone polymerization.The Pt(IV)prodrug and AIE molecule are simultaneously copolymerized as hydrophobic units and blocked with a hydrophilic PEG.Then a biocompatible multi-block copolymer(CTPED)was constructed.The prepared copolymer has the function of fluorescence imaging and can be used to track the position and release behavior of drugs in the cells.In order to enhance the functionality of the material,we further load doxorubicin(DOX)into the polymer CTPED.The loaded DOX can be combined with the two small molecules in CTPED to increase the anti-tumor ability,reduces the toxicity of the material to the system.At the same time,the drugs release behavior can be tracked by fluorescence imaging.And then,we have successfully developed novel single-stimulus and dual responsive dual-drug nanoparticles based on MSN-polymer hybrided mesoporous silica.Both Cur and Pt(py)in MSN-Pt-PEG@Cur could be photoactivated by irradiation,reaching efficient intracellular drug release for platinum(IV)prodrug and simultaneously generating instant ROS from Cur.In comparison with chemotherapy of free anti-cancer drugs and single photoactivated therapy,MSN-Pt-PEG@Cur exhibited increased photoactivated cytotoxicity.Therefore,the usage of light stimulus dual-drug responsive nanoparticles is a promising strategy for dual-drug control released,selective responsiveness and combinational photoactivated therapy in the future.