Cyclodextrin-Functionalized Gold Nanorods Loaded with Meclofenamic Acid for Improving N6-Methyladenosine-Mediated Second Near-Infrared Photothermal Immunotherapy

• DOI: 10.1021/acsami.2c09978
• Publication Date: 2022-09-02T15:13:21Z
• Authors: Jianhua Liu; Yue Song; Yiqiao Wang; Mingda Han; Chunxi Wang; Fei Yan
• Keywords: Cancer Immunotherapy

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 dose-limiting toxicity are the major limitations immunotherapy. Nanoparticle-based photothermal can amplify antitumor immune responses, although poor tumor penetration depth near-infrared radiation (NIR) immunosuppressive microenvironment significantly dampen effects. We designed a nanoplatform based gold nanorods for NIR-II-mediated therapy (PTT) combined with N6-methyladenosine (m6A) demethylase inhibition achieve enhanced against prostate cancer. The GNRs were assembled layer by polystyrenesulfonate as interconnecting then coated cationic polymer γ-cyclodextrin (CD)-cross-linked low-molecular-weight polyethylenimine that was conjugated an 8-mer peptide targeting tumor-specific gastrin-releasing receptor. m6A RNA inhibitor meclofenamic acid (MA) loaded into CD cavity through hydrophobic interactions. GNR-CDP8MA specifically targeted cells selectively accumulated at site vivo. In addition, almost completely ablated cancer cell-derived upon 1208 nm laser irradiation. Mechanistically, NIR-II triggered release MA from GNR-CDP8MA, which increased global mRNA methylation decreased stability PDL1 transcripts. Furthermore, GNR-CDP8MA-mediated PTT-induced immunogenic cell death primary consequently immunity activating antigen-presenting dendritic effector T tumors. This study offers insights synergistic PTT effective strategy