Multifunctional Nanoassembly for MRI-Trackable Dendritic Cell Dependent and Independent Photoimmunotherapy

• DOI: 10.1021/acs.nanolett.3c03098
• Publication Date: 2023-09-28T11:00:16Z
• Authors: Bing Xiao; Hongxia Xu; Xiaodan Xu; Yixuan Pan; Xueying Shi; Pengcheng Yuan; Nigel K. H. Slater; Wenjing Sun; Jianbin Tang; Youqing Shen; Jianqing Gao
• Keywords: Immunogenic cell death; Antigenicity

Immunotherapy has emerged as a triumph in the treatment of malignant cancers. Nevertheless, current immunotherapeutics are insufficient addressing tumors characterized by tumor cells' inadequate antigenicity and microenvironment's low immunogenicity (TME). Herein, we developed novel multifunctional nanoassembly termed FMMC through self-assembly indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor 1-methyl-tryptophan prodrug (FM), Ce6, ionic manganese (Mn2+) via noncovalent interactions. The laser-ignited could induce effective immunogenic cell death activate STING/MHC-I signaling pathway, thus deeply sculpting tumor-intrinsic to achieve dendritic (DC)-dependent -independent T responses against tumors. Meanwhile, inhibiting IDO-1, lead immunosuppressive TME reversion an immunoactivated one. FMMC-based phototherapy led up-regulation programmed death-ligand (PD-L1), enhancing sensitivity anti-PD-1 therapy. Furthermore, incorporation Mn2+ into resulted augmented longitudinal relaxivity enhanced MRI for monitoring growth primary lung metastases. Collectively, superior reprogramming performance cells TME, combined with excellent anticancer efficacy capability, made promising immune nanosculptor cancer theranostics.