Beating xenograft liposarcoma using metal selenides with NIR-III photothermal ablation and bioactive selenium derivates

Liposarcoma (LPS) is a rare but heterogeneous tumor characterized by significant variations in therapeutic outcomes with different drugs, inhibitors, and antibodies. Generating high-quality non-specific therapy for the management of LPS is challenging. Herein, we prepared multifunctional titanium diselenides chelated with Gd3+ ions (TiSe2-Gd) for imaging-guided LPS treatments through photothermal therapy (PTT) in the near-infrared III (NIR-III) window and bioeffects of selenium derivates. These nanoagents have an intense NIR-III absorbance and yield a stable and high photothermal conversion through non-radiative decay, achieving tissue-penetrating NIRIII PTT of LPS. The NIR-III PTT and selenium derivates upgrade the expression levels of inflammatory cytokines, including interleukin-113 (IL-113), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha), boosting immune reactions. Moreover, the level of glutathione peroxidase (GSH-PX) is upregulated while the superoxide dismutase (SOD) is downregulated, which strengthens the antioxidant defense. The biodegradation and structural dissociation of these nanoagents in vivo ensure long-term biosafety and excretion via the hepatobiliary and fecal pathways. As a result, this study not only develops NIR-III nanoagents against the patient-derived xenograft (PDX) LPS but also provides insights into novel anti-LPS strategies.