A mitochondria targeting aggregation-induced emission phototheranostic agent for photodynamic synergistic therapy of triple-negative breast cancer.

Abstract

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterized by poor prognosis and high mortality. However, current treatment options remain inadequate, necessitating the urgent development of novel, more effective therapeutic strategies. Here, we utilize amphiphilic DSPE-PEG2000 as a scaffold to co-assemble an anionic π+ self-assembled emission-inducing emitter (photosensitizer, TMP) and an immunostimulant, CpG, via electrostatic adsorption, constructing an effective phototherapeutic diagnostic agent (termed DTC NPs). Notably, the innovatively designed TMP exhibits highly efficient aggregation-induced emission (AIE) properties, mitochondrial targeting capability, effective ROS generation, and low cytotoxicity. Upon 480 nm light irradiation, TMP induces immunogenic cell death (ICD) in tumor cells by generating abundant reactive oxygen species (ROS), thereby enabling photodynamic therapy (PDT). Crucially, intratumoral CpG enrichment stimulates immune factor production, synergistically enhancing ICD effects, promoting dendritic cell (DC) maturation, and facilitating T-cell infiltration. In vivo animal studies demonstrate that the synergistic combination of TMP's PDT activity and CpG's immunotherapeutic effects significantly suppresses tumor growth. Compared to high-dose chemotherapy, it induces more potent immune stimulation and superior therapeutic outcomes against tumors. Furthermore, the combination of DTC NPs with paclitaxel (PTX) markedly enhances therapeutic efficacy. This work represents a promising adjuvant chemotherapy strategy capable of boosting immune activation and therapeutic outcomes against drug-resistant tumors.