Iridium complex-loaded biomimetic vesicles enable enhanced photodynamic therapy and immune modulation

The strategic integration of micro/nano-engineering with controlled optical responses is pivotal for advancing solid tumor therapy. We have constructed a biomimetic nanosystem via the precise encapsulation of a flexible-chain iridium complex (IrC8) within giant plasma membrane vesicles (GPMVs) derived from tumor cells. This micro/nano-scale design leverages the endogenous structure of GPMVs to achieve superior biocompatibility and enhance homologous targeting, resulting in a 4.7% increase in cellular uptake compared to the free complex. The encapsulated IrC8 complex serves as a highly efficient photosensitizer, exhibiting a strong optical response characterized by an aggregation-induced emission enhancement factor (I/I₀) > 10 and a high singlet-oxygen quantum yield (ΦΔ = 0.18). Upon photoactivation, this system generates reactive oxygen species (ROS) with an 18-fold increase in yield, leading to potent phototoxicity with over 90% tumor cell apoptosis. Furthermore, the systematic integration of the vesicular carrier and the photosensitizer initiates a cascade reaction: the photodynamic effect not only directly eradicates tumor cells but also triggers immunogenic cell death (ICD), leading to potent immune activation. This synergistic combination of targeted delivery, photodynamic therapy, and immune stimulation within a single nanosystem demonstrates a remarkable synergistic therapeutic effect against solid tumors.