Related Experiment Video
Updated: Aug 6, 2026
06:50
Mitochondrial Transfer Via Tunneling Nanotubes Between Mesenchymal Stem Cells and Retinal Pigment Epithelium In Vitro
Published on: October 4, 2024
Leveraging Mitochondria-Endoplasmic Reticulum Functional Interplay With an On-Demand Nanoparticle to Boost
Han Chen1,2, Haijing Qu1,2, Yuqing Pan1
1Shanghai Frontiers Science Center of Drug Target Identification and Delivery, National Key Laboratory of Innovative Immunotherapy, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai, China.
Advanced Materials (Deerfield Beach, Fla.)
|July 17, 2026
Summary
This study introduces a novel nanoparticle system that enhances STING activation by releasing mitochondrial DNA and inducing ER stress. This approach boosts antitumor immunity, suppressing tumor growth and recurrence in preclinical models.
Area of Science:
- Immunology
- Nanotechnology
- Cancer Biology
Background:
- Endogenous STING activation by mitochondrial DNA (mtDNA) is a potential cancer immunotherapy strategy.
- Current limitations include weak and transient signaling, hindering robust STING clustering and efficacy.
- Mitochondrial-ER functional interplay is key to modulating STING signaling.
Purpose of the Study:
- To develop an on-demand nanoparticle system to enhance STING activation for cancer immunotherapy.
- To harness mitochondrial-ER interplay by inducing mtDNA release and ER stress.
- To improve STING-TBK1 assembly and downstream signaling for potent antitumor responses.
Main Methods:
- Developed a nanoparticle system for concurrent mtDNA release and ER stress induction.
- Utilized nanoparticles for spatially controlled co-delivery of immunotherapy agents.
- Assessed STING, TBK1, and IRF3 phosphorylation levels.
- Evaluated CD8+, CD4+ T cell infiltration and regulatory T cell (Treg) populations in vivo.
- Tested efficacy in mouse models of breast and colon cancer.
Main Results:
- The nanoparticle system significantly increased STING, TBK1, and IRF3 phosphorylation compared to PBS.
- Performance surpassed the commercial STING agonist MSA-2.
- Achieved potent enhancement of innate and adaptive antitumor immunity in vivo.
- Demonstrated significant increases in CD8+ and CD4+ T cell infiltration and reduction in Tregs.
- Successfully suppressed tumor progression, metastasis, and recurrence in preclinical models.
Conclusions:
- The developed on-demand nanoparticle system effectively enhances STING-based immunotherapy.
- This strategy integrates controlled drug release with organelle-level immune modulation.
- The approach shows significant promise for improving cancer treatment outcomes by boosting antitumor immunity.
Related Concept Videos
01:46Electron Transport Chain: Complex I and II
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
01:27Tumor Immunotherapy
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
01:19Translocation of Proteins into the Mitochondria
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
01:37Mitochondria
Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
01:28The Inner Mitochondrial Membrane
The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria. In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
02:59Animal Mitochondrial Genetics
Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...