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DMSA-coated IONPs trigger oxidative stress, mitochondrial metabolic reprograming and changes in mitochondrial
Neus Daviu1, Yadileiny Portilla1, Marta Gómez de Cedrón2
1Department of Immunology and Oncology and Nanobiomedicine Initiative, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, 28049, Madrid, Spain.
Abstract:
There is increasing interest in modulating the redox homeostasis of tumors since high levels of reactive oxygen species (ROS) make them more vulnerable to changes in these species. Nanomedicine offers promise in this context as such applications may provoke biological responses that induce ROS production. Indeed, iron oxide nanoparticles (IONPs) can induce ROS accumulation through the so-called Fenton reaction of iron, further augmenting the ROS in tumors and overloading the antioxidant system beyond its capacity, thereby driving oxidative stress to a level that is incompatible with cell survival. Here, three different coatings for IONPs were compared to assess their intrinsic capacity to induce ROS production in cells. Of these coatings, dimercaptosuccinic acid-coated IONPs (DMSA-NPs) provoked the strongest ROS production, which was associated with the ability to reprogram the metabolism of cancer cells. This latter phenomenon involved shutting-down oxidative phosphorylation (OXPHOS), shifting mitochondrial morphology towards a more elongated phenotype, reducing the total mitochondrial mass and ultimately, blocking cell proliferation by inducing G0/G1 cell cycle arrest. Consequently, the data obtained highlights the importance of studying the chemical properties of IONPs, presenting DMSA-NPs as a novel tool to induce oxidative stress in cancer cells and alter their cell fate.
Insights
Dimercaptosuccinic acid-coated iron oxide nanoparticles (DMSA-NPs) effectively induce reactive oxygen species (ROS) in cancer cells. This nanomedicine approach reprograms cell metabolism, halting proliferation and offering a novel strategy for cancer treatment.
Area of Science:
- Nanomedicine
- Cancer Biology
- Redox Homeostasis
Background:
- Tumor cells exhibit altered redox homeostasis, making them susceptible to reactive oxygen species (ROS) manipulation.
- Nanoparticles, particularly iron oxide nanoparticles (IONPs), can induce ROS accumulation via the Fenton reaction, potentially overwhelming cancer cell antioxidant systems.
Purpose of the Study:
- To compare the ROS-inducing capacity of three different IONP coatings.
- To investigate the effects of IONPs on cancer cell metabolism and proliferation.
Main Methods:
- Synthesis and characterization of IONPs with different coatings.
- In vitro assessment of ROS production in cancer cells exposed to IONPs.
- Analysis of cellular metabolism, mitochondrial morphology, and cell cycle progression.
Main Results:
- Dimercaptosuccinic acid-coated IONPs (DMSA-NPs) demonstrated the highest ROS production.
- DMSA-NPs treatment led to the shutdown of oxidative phosphorylation (OXPHOS) and altered mitochondrial morphology.
- Cancer cells treated with DMSA-NPs exhibited reduced mitochondrial mass and G0/G1 cell cycle arrest, inhibiting proliferation.
Conclusions:
- The chemical properties of IONP coatings are critical for their biological effects.
- DMSA-NPs represent a novel nanomedicine tool for inducing oxidative stress in cancer cells.
- DMSA-NPs can reprogram cancer cell metabolism, leading to cell cycle arrest and potential therapeutic benefits.
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