Precision USPIO-PEG-SLex Nanotheranostic Agent Targeted Photothermal Therapy for Enhanced Anti-PD-L1 Immunotherapy to Treat Immunotherapy Resistance

作者：Ting Li, Lianshan Guo, Jiaxu Li, Xingyu Mu, Lijuan Liu, Shulin Song, Ningbin Luo, Qi Zhang, Bin Zheng, Guanqiao Jin · 发表于：International Journal of Nanomedicine · 年份：2024 · DOI：10.2147/ijn.s445879 · 被引用次数：12 · 研究领域：Nanoplatforms for cancer theranostics、Cancer Immunotherapy and Biomarkers、Protein Degradation and Inhibitors

Background: The anti-Programmed Death-Ligand 1 (termed aPD-L1) immune checkpoint blockade therapy has emerged as a promising treatment approach for various advanced solid tumors. However, the effect of aPD-L1 inhibitors limited by the tumor microenvironment makes most patients exhibit immunotherapy resistance. Methods: We conjugated the Sialyl Lewis X with a polyethylene glycol-coated ultrasmall superparamagnetic iron oxide (USPIO-PEG) to form UPS nanoparticles (USPIO-PEG-SLe x , termed UPS). The physicochemical properties of UPS were tested and characterized. Transmission electron microscopy and ICP-OES were used to observe the cellular uptake and targeting ability of UPS. Flow cytometry, mitochondrial membrane potential staining, live-dead staining and scratch assay were used to verify the in vitro photothermal effect of UPS, and the stimulation of UPS on immune-related pathways at the gene level was analyzed by sequencing. Biological safety analysis and pharmacokinetic analysis of UPS were performed. Finally, the amplification effect of UPS-mediated photothermal therapy on aPD-L1-mediated immunotherapy and the corresponding mechanism were studied. Results: In vitro experiments showed that UPS had strong photothermal therapy ability and was able to stimulate 5 immune-related pathways. In vivo, when the PTT assisted aPD-L1 treatment, it exhibited a significant increase in CD4 + T cell infiltration by 14.46-fold and CD8 + T cell infiltration by 14.79-fold, along with elevated...