Work

1111 NIR light mediated mechanical destruction of glioma cells to trigger tumor antigen release and potentiate immunogenic cell death

Year: 2026

Type: conference-abstract

Abstract: Background Glioblastomas (GBMs) are immune cold tumors. A combination of immuno-suppressive cells in the tumor microenvironment, dysregulated metabolism, tumor hypoxia and poor neoantigen repertoire protect cancer cells from immune surveillance and destruction. Mechanical destruction of tumor cells by near-infrared (NIR) activated molecular nanomachines can trigger an abundance of tumor antigen release and damage-associated molecular patterns to stimulate a robust anti-tumor immune response.Methods Cy7.5-amine molecular nanomachines (MNM) which convert incident NIR energy into mechanical energy were synthesized as previously described. 1 Human (U87 and U251) and murine (GL261) cancer cells were treated with increasing concentrations (0.125–2 μM) of MNM diluted in complete media. Fluorescence intensity (excitation 760/34; emission 818/40) was recorded to confirm localization of the drug on cancer cells. Subsequently, cancer cells were treated with MNM for 30 minutes. At increasing intervals following drug treatment (immediate, 1 hour, 6 hour or 24 hour), cells were photo-irradiated with 730-nm light (75 mW/cm2) for 10 minutes. 24 hours after treatment cell viability was assessed with trypan blue (0.4%) dye exclusion assay. In parallel, colony forming assay was carried out with increasing concentrations of MNM coupled with light therapy. Colonies were fixed, stained and counted 7 days after treatment. Statistical significance was determined using one-way ANOVA and two-way ANOVA.Results Human and murine glioma cells were found to sequester MNM after pulse dose exposure, with higher concentrations (1 μM, 1.5 μM and 2 μM) persisting even 24 hours later. No dark toxicity was observed and concentrations ≥ 0.250 μM + NIR significantly reduced cell viability (0.250 μM ~ 85%; 0.50 μM ~ 80%; 1-2 μM ~ 20%) ( figure 1). Combination therapy continued to be effective when NIR was applied at increasing intervals after MNM exposure (1 h ~ 20%; 6 h ~ 20%; 24 h ~ 30%) (figure 2). In clonogenic assay, 100% cell killing was recorded in MNM (1 μM, 1.5 μM and 2 μM) + NIR treated groups.Conclusions MNMs trigger mechanical (non-photothermal, non-photodynamic) destruction of glioma cells upon NIR activation. Purely mechanical destruction of cells ensures GBMs can be ablated despite chemo-radio resistance characteristic of the disease. Further, resultant tumor antigen release and massive DAMP efflux can super charge the tumor infiltrating immune cells and the lack of caloric or oxidative stress with this therapy ensures the integrity of liberated tumor antigens.Reference B Li, C Ayala-Orozco, T Si, L Zhou, Z Wang, AA Martí, JM Tour, Divergent Syntheses of Near-Infrared Light-Activated Molecular Jackhammers for Cancer Cell Eradication. Adv. Sci.2024;11:2405965. https://doi.org/10.1002/advs.202405965Abstract 1111 Figure 1MNM + NIR therapy kills glioma cells. Increasing concentrations of MNM (0.250uM - 2uM) upon activation by 730nm NIR light destroy glioma cellsAbstract 1111 Figure 2MNM persists on tumor cells. 2uM MNM persists on tumor cell surface and can be activated over a period of time to trigger cancer cell killing

Source: Journal for ImmunoTherapy of Cancer

DOI: 10.1136/jitc-2026-sitc2026.1111