AntiPD-L1 antibody conjugated Au-SPIOs nanoparticles for enhancing radiosensitivity and activating anti-tumor immune response

To improve the radiation therapy outcomes by inducing more toxicity for tumors and less for normal tissue and switch microenvironment immunosuppressive caused by expression of PD-L1 and tumor-associated macrophages (TAMs) to immunoreactive, we designed a PD-L1-targeted nanoplatform consisting of gold nanoparticles (AuNPs) and superparamagnetic iron oxide nanoparticles (SPIOs)( antiPD-L1-SPIOs@PLGA@Au). AntiPD-L1-SPIOs@PLGA@Au targeted on the B16F10 cell membrane and in cytoplasm, and the association could be reduced by the antibody blocking. In vivo T2-weight image, the best enhancement effect of tumor was achieved two hours after intravenous injection of antiPD-L1-SPIOs@PLGA@Au. Compared with radiation alone, the Do sensitization ratios of antiPD-L1-SPIOs@PLGA@Au was 1.34. The inhibition effect of irradiation combined with antiPD-L1-SPIOs@PLGA@Au was higher than that of radiotherapy alone in the B16F10 subcutaneous tumor model. During the entire observation period, all mice in the antiPD-L1-SPIOs@PLGA@Au group lived longer than 3 weeks. AntiPD-L1-SPIOs@PLGA@Au enhancing radiosensitivity was achieved by increasing ROS production and attenuating DNA damage repair. In vitro and in vivo experiments showed that antiPD-L1-SPIOs@PLGA@Au could promote the polarization of tumor-associated macrophages (TAMs) to M1 and reverse the immunosuppressive regulation induced by TAMs. antiPD-L1-SPIOs@PLGA@Au could increase the expression of CRT in tumor, block the PD-L1/PD pathway, activate CD8+T cells, promote the increase of IFN-γ, TNF-α and IL-12 release, and finally activate the anti-tumor immune response. In conclusion, antiPD-L1-SPIOs@PLGA@Au was proved to have the ability to form targeted imaging and enhance radiosensitivity, block the PD-L1/PD-1 immune checkpoint pathway, reverse the immunosuppressive regulation caused by TAMs, successfully realizing the synergistic effect of radiotherapy combined with immunotherapy.