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Copper Sulfide Nanoparticle-Mediated Photothermolysis Induces Immunogenic Cell Death in Ovarian Cancer Cells

Li, D.; Shi, S.; Cao, Q.; Sood, A. K.; Molldrem, J. J.; Ma, Q.; Li, C.

2025-07-11 immunology
10.1101/2025.07.08.662637 bioRxiv
Show abstract

Immunotherapy has only limited efficacy against ovarian cancer because of dysfunctional T cells in an immunosuppressive tumor microenvironment. Selective photothermolysis is a technique in which short pulsed laser is used to ablate tissue in targeted regions in a precise spatiotemporally controlled manner. This technique allows targeted tissue ablation without damage to surrounding tissue. In the current study, we demonstrated that ovarian cancer cells treated with photothermolysis mediated by near-infrared-absorbing CuS nanoparticles and 15-ns laser pulses were ingested by human monocyte-derived dendritic cells (MoDCs) more efficiently than were ovarian cancer cells treated with ionizing radiation. Moreover, ingestion of ovarian cancer cells treated with CuS NP-mediated photothermolysis promoted MoDC activation. Immature MoDCs that had been exposed to photothermolysis-treated cancer cells caused greater clonal expansion of co-cultured human CD4+ and CD8+ T cells than did immature MoDCs that had been exposed to ionizing radiation-treated tumor cells. These data indicate that photothermolysis may be used to selectively target and destroy tumor cells and cause them to release antigens and danger signals, which can be recognized by DCs to activate T cells.

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