Preparation Of Functionalized AI-MPHA NCs And Its Study Of NO Enhanced Photothermal Therapy On MG-63 Cells Ablation

Osteosarcoma（OS）is a kind of common malignant solid tumor with high mortality,easy recurrence and high degree of malignancy,affecting adolescents usually.Clinical treatments include radiotherapy,chemotherapy and surgical excision.Due to the toxic side effects and bone defects caused by the conventional methods,It’s urgent to achieve efficient osteosarcoma cell ablation through a new way with low-invasive and in-situ.The development and rise of nanotechnology and photothermal therapy provide a new idea for low-injury in situ therapy.However,nanoplatforms with efficient photothermal conversion for the treatment of osteosarcoma have rarely been studied,and the problem of poor efficacy of photothermal therapy（PTT）materials for solid tumors has not been well solved.Therefore,it’s significant to construct a multifunctional nanocomposite with synergistic photothermal ablation on osteosarcoma treatment.Aiming at these problems,this project designed and fabricated nano-platforms（MPHA NCs）based on mesoporous polydopamine（MPDA）compounded nano-hydroxyapatite（n-HAp）by using nano-methods.The loaded Indocyanine green（ICG）and the graft-modified L-arginine（L-Arg）were complexed into MPHA NCs to functionalize the nanocomposite.AI-MPHA NCs could achieve in-situ photothermal ablation of osteosarcoma cells.At the same time,the combination of nitric oxide（NO）producing part enabled AI-MPHA NCs to generate NO,achieving the purpose of NO gas therapy synergistic photothermal therapy.The research results have proved the nanocomposites（MPHA NCs）had a core-shell structure,which was a rod-like structure with a diameter of 370.5 nm.The N₂ adsorption-desorption experiments have shown the porous structure of the material,and the ICG loading experiments have proved its good adsorption capacity.At the same time,the results of XRD,FIRT and UV-Vis tests have proved the successful preparation of AI-MPHA NCs,and the cytotoxicity test have showed the good cytocompatibility of materials.The results of photothermal test have proved the photothermal properties of the nanocomposites had both concentration-dependent and power density-dependent characteristics.With excellent photothermal stability,and the photothermal conversion efficiency could reach 24.9%.Good photothermal conversion could provide the basis for the ablation of osteosarcoma cells.The study of reactive oxygen species（ROS）generation has shown the functionalized AI-MPHA NCs could achieve photo-triggered ROS generation,and with the increase of material concentration and laser power densities,more ROS could be generated.The exploration of the release of nitric oxide from the material has shown that AI-MPHA NCs could achieve controllable release of NO under laser irradiation.Under 1W cm^-2 laser irradiation,250μg mL^-1 of AI-MPHA NCs could release about4×10^-6 mol L^-1 NO.The generation of NO played a synergistic role for the next step of photothermal therapy.The In vitro ablation experiments of osteosarcoma cells has confirmed that both MPHA NCs and AI-MPHA NCs had good photothermal therapy effects,and achieved good cancer cell ablation.More importantly,compared with the photothermal ablation results of pure MPHA NCs,the functionalized AI-MPHA NCs could introduce NO release during photothermal therapy.It solved the problem pure photothermal could not achieve efficient killing of solid tumor tissue.In conclusion,to deal with the problems existing in the ablation of osteosarcoma,the AI-MPHA NCs have been designed in this study to achieve the combination of NO therapy and photothermal therapy for efficiently osteosarcoma cells ablation.And the construction of the AI-MPHA NCs has provided a new approach for osteosarcoma treatment...