Cell-Driven Encapsulation of Chlorophyllin-Based Carbon Dots within Exosomes for Enhanced Photodynamic Therapy: miRNA Profiling Reveals Mechanistic Insights

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 (EXOMSC), with their natural tropism toward t...

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Detalles Bibliográficos
Autores: Besbinar, Omur, Uyar, Recep, Kirbas Cilingir, Emel, Martín-Pardillos, Ana, Hueso, Jose L., Ceylan, Ahmet, Ozgenc, Ozge, Ekim, Okan, Unal, Mehmet Altay, Ari, Fikret, Leblanc, Roger M., Santamaria, Jesus, Yilmazer, Acelya
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Universidad de Zaragoza
Repositorio:Zaguán. Repositorio Digital de la Universidad de Zaragoza
OAI Identifier:oai:zaguan.unizar.es:165154
Acceso en línea:http://zaguan.unizar.es/record/165154
Access Level:acceso abierto
Descripción
Sumario: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 (EXOMSC), 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 EXOMSC through a cell-driven uptake mechanism, creating CD@EXOMSC. 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.