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 (EXO<sub>MSC</sub>), 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<sub>MSC</sub> through a cell-driven uptake mechanism, creating CD@EXO<sub>MSC</sub>. 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.
Authors
- Okan Ekim (ORCID: https://orcid.org/0000-0002-3322-4161)
- Ömür Beşbinar (ORCID: https://orcid.org/0000-0002-1107-7578)
- Mehmet Altay Ünal (ORCID: https://orcid.org/0000-0001-8607-5043)
- Roger M. Leblanc (ORCID: https://orcid.org/0000-0001-8836-8042)
- Ahmet Ceylan (ORCID: https://orcid.org/0000-0001-5878-8775)
- Açelya Yılmazer (ORCID: https://orcid.org/0000-0003-2712-7450)
- Ana Martín-Pardillos (ORCID: https://orcid.org/0000-0003-1717-8465)
- Recep Uyar (ORCID: https://orcid.org/0000-0002-7788-6685)
- Fikret Arı (ORCID: https://orcid.org/0000-0002-6104-4467)
- José L. Hueso (ORCID: https://orcid.org/0000-0002-4546-4111)
- Jesús Santamaría (ORCID: https://orcid.org/0000-0002-8701-9745)
- Özge ÖZGENÇ
Institutions
- University of Miami (US)
- Ankara University (TR)
- University of Electronic Science and Technology of China (CN)
- Universidad de Zaragoza (ES)
- Instituto de Salud Carlos III (ES)
- Faculty (United Kingdom) (GB)
- PLA Electronic Engineering Institute (CN)
- Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (ES)
- Department of Embryology (US)
- Université Bourgogne Franche-Comté (FR)
- Engineering (Italy) (IT)
- Instituto de Nanociencia y Materiales de Aragón (ES)
- IQ Samhällsbyggnad (SE)
- Instituto de Investigación Sanitaria Aragón (ES)
- Stem Cell Institute (PA)
- Turkish Thoracic Society (TR)
- Guilin University of Electronic Technology (CN)
Publication Details
- Journal
- ACS Applied Materials & Interfaces
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1021/acsami.5c18555
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 0.00