| Photothermal/photodynamic therapy(PTT/PDT)can not only directly kill tumor cells,but also trigger immunogenic cell death of tumors in situ.Whereas it is virtually impossible to eradicate the tumor due to the intrinsic resistance and inefficient anti-tumor immunity.Therefore,this study synthesized a bimetallic infinitely coordinated nanopolymer(TA-Fe/Mn-OVA@MB NPs)through metal coordination andπ-πstacking interaction.TA-Fe/Mn-OVA@MB NPs which combine efficient photothermal ablation and photodynamic therapy can effectively kill local solid tumor cells.Meanwhile,these TA-Fe/Mn-OVA@MB NPs are capable of promoting maturation and antigen presentation of dendritic cells(DCs)via manganese-mediated cGAS-STING pathway activation,finally help the differentiation of cytotoxic T lymphocyte(CTLs)and effective memory CD8~+T cells,so enhance anti-tumor immune activation.In conclusion,this research offers a versatile metal-polyphenol nanoplatform with integration of functional metals and therapeutic molecules and provides a promising strategy for combination of local phototherapy and antitumor immune activation.Method:1.Novel bimetallic infinite coordination nanopolymers(TA-Fe/Mn-OVA@MB NPs)were synthesized using model antigen ovalbumin(OVA)as a template to assemble tannic acid(TA)and bi-metal,supplemented with methylene blue(MB)surface absorption.2.The physicochemical characterization of TA-Fe/Mn-OVA@MB NPs was validated by Scanning electron microscopy,Transmission electron microscopy,Marvin particle size analysis,Fourier transform infrared spectroscopy,and High-performance liquid chromatography.3.The biocompatibility of TA-Fe/Mn-OVA@MB NPs was validated by hemolysis experiments and CCK-8 cell experiments.4.The photothermal and photodynamic properties of TA-Fe/Mn-OVA@MB NPs in vitro were evaluated by infrared thermal imaging cameras,UV visible spectrophotometers,and CCK-8cell experiments.5.The anti-tumor effect of TA-Fe/Mn-OVA@MB NPs in vivo was evaluated by establishing tumor model mice under different treatment.6.The magnetic resonance and thermal imaging functions of TA-Fe/Mn-OVA@MB NPs in vivo were characterized by magnetic resonance and infrared thermal imaging cameras.7.The anti-tumor effect of the TA-Fe/Mn-OVA@MB NPs in vivo and in vitro was investigated by Flow cytometry.Resultant:1.Novel bimetallic infinite coordination nanopolymers(TA-Fe/Mn-OVA@MB NPs)were developed via metal-coordination andπ-πstacking interaction.2.The morphology of TA-Fe/Mn-OVA@MB NPs is granular and average particle size is 161nm.3.The TA-Fe/Mn-OVA@MB NPs solution has good dispersion and biocompatibility.4.TA-Fe/Mn-OVA@MB NPs with PTT and PDT performance can effectively inhibit the growth of tumor cells.5.TA-Fe/Mn-OVA@MB NPs can effectively inhibit the growth of solid tumors in vivo.6.TA-Fe/Mn-OVA@MB NPs could be used as T1/T2-weighted MR contrast agent to guide in vivo therapy.7.TA-Fe/Mn-OVA@MB NPs can promote maturation of DCs by cGAS-STING signaling pathways and so enhance antitumor immune effect.Conclusion:In summary,NIR responsive bimetallic infinite coordination nanopolymers(TA-Fe/Mn-OVA@MB NPs)have been prepared via metal-coordination andπ-πstacking interaction in this research.The synthesized TA-Fe/Mn-OVA@MB NPs have a spherical appearance,good dispersity in water and biocompatibility.Under 808/660 nm combined laser irradiation,the TA-Fe/Mn-OVA@MB NPs with synergetic photothermal and photodynamic performance can effectively kill tumor cells and trigger the release of tumor antigens.More importantly,the TA-Fe/Mn-OVA@MB NPs can promote the maturation and antigen-cross-presentation of DCs via manganese-mediated cGAS-STING pathway activation,and subsequently facilitate the expansion of CTL and the differentiation of effector memory T lymphocyte in the peripheral lymphoid organs.Overall,this metal-polyphenol nanoplatform with integration of therapeutic proteins and small molecule compounds provides a promising strategy for combination of local phototherapy and antitumor immune response. |
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