ATP-exhausted nanocomplexes for intratumoral metabolic intervention and photoimmunotherapy. (May 2022)

• Record Type: Journal Article
• Authors: Yu, Mian; Zeng, Weiwei; Ouyang, Yaqi; Liang, Shu; Yi, Yunfei; Hao, Huisong; Yu, Jiayin; Liu, Yang; Nie, Yichu; Wang, Tianqi; Deng, Yang; Wu, Meiying
• Is Part Of: Biomaterials. Volume 284(2022)
• Publication Date: 2022-05
• Subjects: Metabolic intervention -- Photoimmunotherapy -- ATP depletion -- Oxidative stress -- Immunogenic cell death; ICD immunogenic cell death -- DAMPs damage-associated molecular patterns -- ATP adenosine triphosphate -- ROS reactive oxygen species -- 2-ICA imidazole-2-carboxaldehyde -- ICG indocyanine green -- TrxR2 thioredoxin reductase-2 -- PTT photothermal therapy -- DAPI 4′, 6-Diamidino-2-phenylindole -- PEI polyethyleneimine -- DCs dendritic cells -- HMGB1 high mobility group box 1 -- CRT calreticulin; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2022.121503
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: Tumor cells reprogram the metabolic pathways to acquire abundant nutrients and sustain malignant proliferation. This fierce metabolic competition in tumor ecosystem has been uncovered to be associated with tumor microenvironmental immunosuppression. Here we develop an adenosine triphosphate (ATP)-exhausted nanocomplex (IR@ZIF-RGD) to intervene in tumor energy metabolism and regulate tumor immune microenvironment. IR@ZIF-RGD could effectively deplete intracellular ATP and inhibit ATP synthesis by ATP-responsive ZIF-90 and siRNA targeting thioredoxin reductase-2, respectively, thus leading to tumor metabolism disorders and immunosuppressive reversion. Meanwhile, IR@ZIF-RGD induced oxidative stress and ICG triggered photothermal therapy could provoke potent immunogenic cell death to enhance antitumor immunogenicity. Such a photo-immunometabolic nanocomplex has been demonstrated to be an efficient vaccine to elicit protective anticancer immune response in vivo, achieving suppressed growth of both primary and abscopal tumors, as well as inhibited tumor metastasis.