Near-infrared orthogonal excitation lanthanide theranostic nanoplatform for NIR-II-L imaging-guided photodynamic therapy via synergistical pyroptosis and apoptosis pathway.

Abstract

Photodynamic therapy (PDT) that induces pyroptosis at the cell membrane has emerged as a promising paradigm for cancer immunotherapy. However, the rapid and precise induction of pyroptosis remains a significant challenge. To address this, we developed a near-infrared orthogonal excitation lanthanide theranostic nanoplatform based on lanthanide doped nanoparticles conjugated with curcumin (CUR) and cyclo(RGD-DPhe-K) peptide (LnNP@CUR-RGD). This platform enables deep-tissue, NIR-II-L imaging-guided PDT that concurrently initiates both pyroptosis and apoptosis. Upon 808 nm excitation, fluorescence at 1530 nm from LnNP@CUR-RGD allows for real-time in vivo tracking and monitoring of its localization to the cell membrane or lysosome. After subsequently switching to 940 nm excitation, the produced 362 nm emission activates CUR to generate singlet oxygen (¹O₂). This process initiates a dual-death mechanism: cell membrane-involved pyroptosis and lysosome-involved apoptosis, which synergistically potentiate the anti-tumor immune response. Notably, this nanoplatform achieves efficient antitumor therapy within 15 min of systemic administration, a significant acceleration compared to the 6 h required for conventional apoptosis-based PDT. This work demonstrates the considerable potential of NIR-light-triggered, targeted theranostic platforms for precise imaging-guided cancer therapy.