Cyclodextrin-Functionalized Gold Nanorods Loaded with Meclofenamic Acid for Improving N 6 -Methyladenosine-Mediated Second Near-Infrared Photothermal Immunotherapy.
ACS applied materials & interfaces(2022)
摘要
Cancer immunotherapy has achieved considerable clinical progress in recent years on account of its potential to treat metastatic tumors and inhibit recurrence. However, low patient response rates and dose-limiting toxicity are the major limitations of immunotherapy. Nanoparticle-based photothermal immunotherapy can amplify antitumor immune responses, although poor tumor penetration depth of near-infrared radiation (NIR) and the immunosuppressive tumor microenvironment significantly dampen its effects. We designed a nanoplatform based on gold nanorods for NIR-II-mediated photothermal therapy (PTT) combined with -methyladenosine (mA) demethylase inhibition to achieve enhanced photothermal immunotherapy against prostate cancer. The GNRs were assembled layer by layer with polystyrenesulfonate as the interconnecting layer and then coated with a cationic polymer of γ-cyclodextrin (CD)-cross-linked low-molecular-weight polyethylenimine that was conjugated to an 8-mer peptide targeting the prostate tumor-specific gastrin-releasing peptide receptor. The mA RNA demethylase inhibitor meclofenamic acid (MA) was then loaded into the CD cavity through hydrophobic interactions. GNR-CDP8MA specifically targeted the prostate tumor cells and selectively accumulated at the tumor site . In addition, GNR-CDP8MA almost completely ablated prostate cancer cell-derived tumors upon 1208 nm laser irradiation. Mechanistically, NIR-II triggered the release of MA from GNR-CDP8MA, which increased global mRNA mA methylation and decreased the stability of PDL1 transcripts. Furthermore, GNR-CDP8MA-mediated PTT-induced immunogenic cell death in the primary tumor and consequently enhanced antitumor immunity by activating the antigen-presenting dendritic cells and tumor-specific effector T cells in the metastatic tumors. This study offers insights into synergistic mA RNA methylation and PTT as an effective strategy for cancer immunotherapy.
更多查看译文
关键词
N6-methyladenosine,RNA methylation,gold nanorods,immunotherapy,photothermal therapy
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要