Cell-Driven Encapsulation of Chlorophyllin-Based Carbon Dots within Exosomes for Enhanced Photodynamic Therapy: miRNA...

Exosomes, nanoscale extracellular vesicles, have emerged as promising carriers in drug delivery due to their ability to bypass biological barriers, low toxicity, high stability, and intrinsic targeting capabilities. Mesenchymal stem-cell-derived exosomes (EXO_MSC), with their natural tropism toward the tumor microenvironment, offer an ideal platform for enhancing therapeutic cargo delivery. In this study, we demonstrate an approach where red-emission chlorophyll-based carbon dots (Chl-CDs) were encapsulated within EXO_MSC through a cell-driven uptake mechanism, creating CD@EXO_MSC. These exosomes achieved superior photodynamic therapy (PDT) efficacy, requiring 40 times less nanomaterial compared to freestanding Chl-CDs. Mechanistic insights from glioblastoma cell miRNA profiling revealed that the enhanced efficacy was mediated by the regulation of efflux transporter genes, oxidative stress responses, and endocytosis pathways. This work highlights the synergistic potential of combining photosensitizers and miRNA-rich exosomes to achieve targeted and sustained therapeutic delivery, paving the way for a multifaceted approach in cancer therapy.