Related Experiment Video
Updated: Sep 8, 2025
Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
Disulfidptosis Nanoinducer Interrupts Tumor Metabolic Privilege to Boost Sustained Immunotherapy
Yapeng Xu1, Xiaoqi Ming1, Jinxiu Qi1
1Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
Abstract:
Malignant tumor metabolic reprogramming drives proliferation and immune evasion by hijacking essential nutrients and shaping an immunosuppressive microenvironment. Although targeting tumor metabolism offers therapeutic promise, selectively modulating aberrant metabolic pathways without affecting normal cells remains a major challenge. Disulfidptosis, a recently identified form of metabolism-dependent regulated cell death, may offer an avenue for metabolic disruption; however, its immunomodulatory potential remains unexplored. Here, a disulfidptosis nanoinducer (CYBC NPs), which was constructed with cancer cell membrane-camouflaged nanoplatform coloaded with cystine and the GLUT1 inhibitor BAY-876, was designed to selectively induce disulfidptosis in triple-negative breast cancer cells. By concurrently blocking glucose uptake and supplementing cystine, CYBC NPs triggered disulfidptosis-mediated cytoskeletal collapse, relocated tumor metabolic fluxes, and induced immunogenic cell death. This metabolic perturbation promoted dendritic cell maturation, M1-like macrophage polarization, and cytotoxic T lymphocyte activation, thereby reversing ITME and suppressing tumor growth. Notably, CYBC NPs elicited robust, nonexhausted antitumor immunity and generated durable immune memory, effectively preventing tumor recurrence and metastasis. Together, our study demonstrated the implementation of disulfidptosis as a standalone immunotherapeutic strategy, offering a paradigm shift in metabolism-driven cancer immunotherapy.
Insights
This study introduces a novel nanoinducer that selectively triggers disulfidptosis in cancer cells, reprogramming tumor metabolism to activate anti-tumor immunity and prevent recurrence. This approach offers a new strategy for metabolism-driven cancer immunotherapy.
Area of Science:
- Oncology
- Immunology
- Nanotechnology
- Metabolic Engineering
Background:
- Tumor metabolic reprogramming fuels cancer growth and immune evasion.
- Targeting tumor metabolism is therapeutically promising but challenging due to selectivity issues.
- Disulfidptosis, a regulated cell death pathway, offers potential for metabolic disruption, but its immunomodulatory effects are unknown.
Purpose of the Study:
- To explore the immunomodulatory potential of disulfidptosis.
- To develop a targeted nanoinducer for selective disulfidptosis induction in triple-negative breast cancer.
- To investigate the therapeutic efficacy of disulfidptosis induction in reversing the tumor microenvironment and suppressing tumor growth.
Main Methods:
- Construction of a cancer cell membrane-camouflaged nanoplatform (CYBC NPs) co-loaded with cystine and GLUT1 inhibitor BAY-876.
- Selective induction of disulfidptosis in triple-negative breast cancer cells by blocking glucose uptake and supplementing cystine.
- Assessment of metabolic flux changes, immunogenic cell death, immune cell activation (dendritic cells, macrophages, T lymphocytes), and in vivo tumor suppression.
Main Results:
- CYBC NPs successfully induced disulfidptosis, leading to cytoskeletal collapse and altered tumor metabolic fluxes.
- Metabolic perturbation via CYBC NPs promoted immune cell maturation and activation, reversing the immunosuppressive tumor microenvironment.
- Treatment with CYBC NPs elicited robust, non-exhausted anti-tumor immunity, generated durable immune memory, and prevented tumor recurrence and metastasis.
Conclusions:
- Disulfidptosis can be effectively implemented as a standalone immunotherapeutic strategy.
- Metabolism-driven cancer immunotherapy can be advanced by leveraging disulfidptosis.
- The developed nanoinducer offers a promising approach for targeted cancer treatment with durable immune memory.
Related Concept Videos
01:27Tumor Immunotherapy
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:17The Tumor Microenvironment
02:56Treatment Resistant Cancers
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...