Journal Article

Combination of ferroptosis and pyroptosis dual induction by triptolide nano-MOFs for immunotherapy of Melanoma

Xia, Xinhua, Xu, Rubing, Guo, Qiuyan, Deng, Guoyan, Wang, Shengmei, Lin, Peng

2023

Overview

Immunotherapy has good potential to eradicate tumors in the long term. However, due to the low immunogenicity of tumor cells, current cancer immunotherapies are not effective. To address this limitation, we constructed a BSA-FA functionalized iron-containing metal-organic framework (TPL@TFBF) that triggers a potent systemic anti-tumor immune response by inducing ferroptosis and pyroptosis in tumor cells and releasing large quantities of damage-associated molecular patterns (DAMPs) to induce immunogenicity, and showing excellent efficacy against melanoma lung metastases in vivo. This nanoplatform forms a metal-organic framework through the coordination between tannic acid (TA) and Fe 3+ and is then loaded with triptolide (TPL), which is coated with FA-modified BSA. The nanoparticles target melanoma cells by FA modification, releasing TPL, Fe 3+ and TA. Fe 3+ is reduced to Fe 2+ by TA, triggering the Fenton reaction and resulting in ROS production. Moreover, TPL increases the production of intracellular ROS by inhibiting the expression of nuclear factor erythroid-2 related factor (Nrf2). Such simultaneous amplification of intracellular ROS induces the cells to undergo ferroptosis and pyroptosis, releasing large amounts of DAMPs, which stimulate antigen presentation of dendritic cells (DCs) and the proliferation of cytotoxic T lymphocytes (CD4+/CD8 + T cells) to inhibit tumor and lung metastasis. In addition, combining nanoparticle treatment with immune checkpoint blockade (ICB) further inhibits melanoma growth. This work provides a new strategy for tumor immunotherapy based on various combinations of cell death mechanisms.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Acids / Advanced 2D nanomaterials for biomedical applications / Analysis / Antigen presentation / Antigens / Apoptosis / Biotechnology / Cancer / Cancer immunotherapy / Cancer therapies / Care and treatment / CD4 antigen / CD8 antigen / Cell death / Cell Line, Tumor / Cell proliferation / Chemistry / Chemistry and Materials Science / Chemotherapy / Clinical outcomes / Cytokines / Cytotoxicity / Damage patterns / Dendritic cells / Development and progression / Drug delivery systems / Drug resistance / Drug therapy / Ethylenediaminetetraacetic acid / Fe3 / Ferroptosis / Health aspects / Humans / Immune checkpoint inhibitors / Immune response / Immune system / Immunogenicity / Immunotherapy / Intracellular / Iron / Life sciences / Lung cancer / Lung Neoplasms - drug therapy / Lungs / Lymphocytes / Lymphocytes T / Medical prognosis / Melanoma / Melanoma - drug therapy / Metal-organic framework / Metal-Organic Frameworks / Metastases / Metastasis / Methylene blue / Molecular Medicine / Nanoparticles / Nanotechnology / Neoplasms / Patient outcomes / Prognosis / Proteins / Pyroptosis / Reactive Oxygen Species / Releasing / Skin cancer / T cells / Tannic acid / Testing / Toxicity / Triptolide / Tumor cells / Tumor immunotherapy / Tumor necrosis factor-TNF / Tumors