Researchers at Tohoku University have developed a multifunctional nanoparticle platform that eradicated drug-resistant triple-negative breast tumors in mice. The study, published in Advanced Science, describes a gallium-based liquid metal nanocomposite coated with whole-blood components to evade immune clearance and accumulate in tumors at five times the rate of conventional nanoparticles.
The platform, designated B-LM-DMX-αCD25, integrates three synchronized mechanisms. Anti-CD25 antibodies on the particle surface selectively deplete regulatory T cells (Tregs) inside the tumor, removing a key immunosuppressive barrier. Near-infrared laser irradiation then heats the tumor to 58°C within five minutes, inducing immunogenic cell death and releasing tumor antigens. Finally, laser activation releases the STING agonist DMX, which promotes dendritic cell maturation and interferon-β production to drive cytotoxic T cell responses.
In orthotopic mouse models of drug-resistant triple-negative breast cancer, the treatment achieved 100% complete tumor regression and suppressed pulmonary metastases by more than 90%. Median survival extended beyond 70 days. Molecular analysis showed a more than 13-fold increase in CD3-positive T cells and an 11-fold increase in dendritic cells within treated tumors, confirming robust immune activation.
Triple-negative breast cancer lacks targetable receptors and responds poorly to immunotherapy, partly because high Treg infiltration suppresses anticancer immunity. By combining Treg depletion, photothermal ablation, and innate immune activation in a single construct, the researchers converted an immunologically "cold" tumor microenvironment into one that supports systemic antitumor immunity.
The blood-camouflage strategy uses autologous blood components to mask the nanoparticles as "self," reducing immune clearance without complex synthetic coatings. The team notes this biomimetic approach could simplify translation to other solid tumors where Treg-mediated immunosuppression limits immunotherapy efficacy.
Future work includes adapting the platform for pancreatic and ovarian cancers, developing formulations compatible with NIR-II lasers to treat deeper tumors, and conducting GLP-compliant repeat-dose toxicology studies as part of a preclinical package toward clinical translation.
Blood-camouflaged nanoparticles defeat drug-resistant breast tumors in mouse model
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