NIR-triggered on-site NO/ROS/RNS nanoreactor: Cascade-amplified photodynamic/photothermal therapy with local and systemic immune responses activation

Photothermal and photodynamic therapies (PTT/PDT) hold promise for localized tumor treatment, yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune activation. Addressing these challenges, we present a novel near-infrared (NIR)-triggered RNS nanoreactor (PBNO-Ce6) to amplify the photodynamic and photothermal therapy efficacy against triple-negative breast cancer (TNBC). The designed PBNO-Ce6 combines sodium nitroprusside-doped Prussian Blue nanoparticles with Chlorin e6 to enable on-site RNS production through NIR-induced concurrent NO release and ROS generation. This not only enhances tumor cell eradication but also potentiates local and systemic antitumor immune responses, protecting mice from tumor rechallenge. Our in vivo evaluations revealed that treatment with PBNO-Ce6 leads to a remarkable 2.7-fold increase in cytotoxic T lymphocytes and a 62% decrease in regulatory T cells in comparison to the control PB-Ce6 (Prussian Blue nanoparticles loaded with Chlorin e6), marking a substantial improvement over traditional PTT/PDT. As such, the PBNO-Ce6 nanoreactor represents a transformative approach for improving outcomes in TNBC and potentially other malignancies affected by similar barriers.