Cancer Cell Membrane Encapsulated Biomimetic-Nanoparticles For Tumor Photothermal Enhanced Immunotherapy

In recent years,cancer immunotherapy has emerged as a key intervention strategy,bringing new hope for effective tumor treatment.Immunotherapy stimulates the body’s immune system,activates autoimmune cells,and specifically recognizes and destroys malignant tumor cells.Its greatest advantage is that it cannot only eliminate the primary tumor,but also inhibit the metastasis and recurrence of the tumor.However,due to the low immunogenicity of tumor cells and insufficient infiltration of T lymphocytes in tumors,only some patients respond to single immunotherapy.Therefore,it is difficult to produce a significant anti-tumor effect only by relying on a single immunotherapy,and immunotherapy is usually combined with other treatment methods to improve the comprehensive anti-tumor treatment effect.Photothermal therapy(PTT)is a new therapeutic method for thermal ablation of solid tumors by using photosensitizers to convert light energy into heat energy.PTT has the advantages of non-invasive,space-time controllability and low toxicity to normal tissues.In recent years,many studies have proved that tumors secrete damage-related molecular patterns and tumor-related antigens when receiving hyperthermia,which is helpful to improve the immunogenicity of tumors.Therefore,the combination of PTT and immunotherapy provides great potential in eradicating primary tumors and inhibiting tumor metastasis and recurrence.Most drugs require efficient transport carriers to deliver the drug to the target site.As a top-down method,the complex composition of proteins,antigens,and other components on the entire cell membrane surface can be retained on the NPs,endowing it with properties such as targeting ability,ligand recognition,long circulation,and immune evasion,thus providing a promising nanoplatform for drug delivery and vaccination.In conclusion,we developed a cancer cell membrane-coated biomimetic nanoparticle to further enhance the immunosuppression of primary tumors and distant metastasis after PTT,specifically as follows:Part I: Amphiphilic polymer F127 was used to coat the photothermal agent indocyanine green(ICG)and the immunosuppressant NLG919 nanoparticles(FIN)to realize the synergistic treatment of PTT and immunotherapy.Then introduce 4T1 cancer cell membrane(CM)on the surface of FIN to form bionic nanoparticles CFIN,which endows nanoparticles with the ability of homologous targeting,increases the accumulation of drugs in tumor sites and improves the therapeutic effect.The successful encapsulation of cancer cell membrane was proved by the characterization of optical properties,morphology and surface protein of CFIN.Using infrared thermal imager to record the temperature change of CFIN after continuous laser irradiation,it is proved that CFIN has excellent photothermal performance.To explore the therapeutic effect of CFIN on tumor at cytological level,the in vitro uptake experiment shows that CFIN can be successfully absorbed by cells,and it shows the ability of homologous targeting in 4T1 cells.MTT assay and live/death staining assay verified that CFIN had a killing effect on cancer cells under laser irradiation.The result of HPLC shows that NLG919 can effectively inhibit the degradation of tryptophan.Flow cytometry was used to evaluate that CFIN-triggered PTT can induce cellular immunogenic death and promote DCs maturation rate and T cell activation.Part II: 4T1 tumor-bearing mouse model was established to evaluate the therapeutic effect of CFIN.The distribution of CFIN in vivo was studied by in vivo fluorescence imaging,and the thermal imaging experiment proved that CFIN had excellent photothermal effect.Measurement of tumor volume showed that CFIN could not only ablate the primary tumor in mice,but also inhibit the growth of distant tumors.It was verified by HPLC that CFIN could effectively inhibit the action of IDO-1 enzyme.The maturation of dendritic cells induced by CFIN in mice and the infiltration of T lymphocytes in tumors were evaluated by flow cytometry.Finally,the experiment of tumor prevention proved that CFIN had the function of tumor vaccine.