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

TL;DR

This study shows how exosomes from stem cells can deliver light-sensitive carbon dots for better cancer treatment, using miRNA to understand how it works.

Contribution

A cell-driven method to encapsulate chlorophyllin-based carbon dots in exosomes, enhancing photodynamic therapy with reduced nanomaterial dosage.

Findings

CD@EXOMSC achieved 40 times higher photodynamic therapy efficacy compared to free Chl-CDs.

miRNA profiling revealed regulation of efflux transporters, oxidative stress, and endocytosis pathways as key mechanisms.

EXOMSC's tumor-targeting ability and miRNA content improve therapeutic delivery and retention.

Abstract

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.

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