Work

Near infrared II excitation conjugated polymers-based phototheranostic nanoplatform for hyperthermia-enhanced ferroptosis and immunotherapy

Year: 2025

Type: article

Abstract: Ferroptosis has the potential to induce immunogenic cell death (ICD) and remodel the immunosuppressive tumor microenvironment (TME). However, intracellular antioxidant glutathione (GSH) inhibits the efficacy of ferroptosis. Consequently, enhancing iron ion uptake while simultaneously depleting GSH presents a promising strategy to improve ferroptosis efficacy. Herein, we have developed phenylboronic acid-modified near infrared II photothermal therapy (NIR-II PTT) conjugated polymers DPP-CPDT-PBA (DCP), which co-load Fe 2+ and GSH scavenger cisplatin (Pt), and encapsulate them within an amphiphilic DSPE-mPEG 2000 to finally construct nanoplatform DCP@Pt@Fe. The formulated DCP@Pt@Fe exhibits outstanding NIR-II photothermal property and NIR-II imaging tracking capability. The thermo- and acidic TME-responsive release of Pt and Fe 2+ synergistically induces ferroptosis in cancer cells through Pt-mediated GSH consumption by forming stable Pt-GSH complexes and Fe 2+ -driven reactive oxygen species (ROS) generation via NIR-II PTT-enhanced Fenton reactions. Notably, ferroptotic tumor cells exhibit high immunogenicity, reprogram tumor-associated macrophage polarization, promote dendritic cell maturation, mobilize T cell activation, and significantly reverse the immunosuppressive TME. Simultaneously, interferon-γ (IFN-γ) produced by tumor-infiltrating immune cells inhibits SLC7A11 expression in cancer cells, which contributes to the ferroptosis therapeutic efficacy. Consequently, our nanoplatform DCP@Pt@Fe effectively eradicates ovarian cancer via synergistic NIR-II-PTT/ferroptosis/immunotherapy, providing an exciting new avenue for therapeutic interventions. • Our conjugated polymers DCP possess excellent NIR-II photothermal performance, NIR-II imaging tracking capacity, and controllable co-loading property for Fe 2+ and Pt. • DCP@Pt@Fe enhances ferroptosis efficacy through photothermal-accelerated Fe 2+ -driven Fenton reactions and Pt-mediated glutathione consumption. • DCP@Pt@Fe significantly reverses the immunosuppressive tumor microenvironment by triggering potent immunogenic cell death and eliciting robust anti-tumoral immunity.

Source: Materials Today Bio

DOI: 10.1016/j.mtbio.2025.102435