Synthesis Of Bi@MOFs-PEG Nanomaterials For Tumor Thermo-chemotherapy

Chemotherapy is considered to be the most effective and widely used anti-cancer method in clinic at the present stage,and a variety of chemotherapeutic drugs are continuously promoted to clinical practice.Meanwhile,as an emerging therapy technique,photothermal therapy has a good effective killing effect on tumor,with non-invasive and minimal side effects.It is expected to replace traditional antibiotics and surgical treatment in some aspects,but its therapeutic effect has certain limitations and easy to relapse.Therefore,building an “intelligent” new diagnosis and treatment platform with multiple diagnostic and therapeutic functions may be a feasible way to achieve effective anti-tumor.Up to now,many nanocomposites have been fabricated based on different high-surface-area claddings(such as: mesoporous silica,liposomes,and vesicles,etc.)and various photothermal materials(such as precious metals,transition metal sulfide and carbon materials,etc.)for combined chemotherapy and photothermal therapy,and a effective drug targeting and controlled release.However,due to the limitation of drug carriers and photothermal materials,the obtained therapeutic effect and the corresponding toxic and side effects are still not satisfactory.To enhance the anti-cancer effect,Bi@MOFs-PEG NPs composite nanoparticles(Bi@MOFs-PEG NPs)based on Bi NPs,MOFs and PEG were designed in this dissertation to realize the collaborative diagnosis,photothermal therapy and chemotherapy under the guidance of infrared thermal imaging.Aim at the shortcomings of Bi NPs,such as low effective drug-loading capacity,poor physiological stability and photothermal cycling stability,we used zeolite imidazole ester organic framework-8 and polyethylene glycol to coat Bi NPs layer by layer to construct a stable porous core-shell structure.The Bi@MOFs-PEG NPs maintained high light absorption at 808 nm,with significant light heating effect and good photothermal conversion efficiency(~28.9%).Moreover,compared with Bi NPs,its physiological stability and photothermal cycle stability have been greatly improv ed.In addition,the porous MOFs coating layer endowing the material with a considerable drug load(~13.7%,mass%),the coating layer could be disintegrated under acid action and near-infrared laser,enabling the drug to be fully released(~90%).It has the potential to realize photothermal combined chemotherapy.Through evaluation of the photothermal therapy,chemotherapy and thermo-chemotherapy performance at the cell and animal levels,the Bi@MOFs-PEG/DOX NPs were revealed to realize synergistic treatment of photothermal therapy and chemotherapy,presenting significantly improved therapeutic effect compared with the single treatment.More importantly,in the process of photothermal therapy and thermochemotherapy,high-performance near-infrared photothermal imaging function can be provided to monitor the temperature changes.Excellent biocompatibility of the NPs was also proved by in vivo and in vitro toxicity tests.Therefore,the multifunctional Bi@MOFs-PEG/DOX NPs have promising clinical application potential in the field of tumor diagnosis and treatment.