Speaker
Description
Extracellular vesicles (EVs) have become recognized as promising natural nanocarriers for targeted drug delivery owing to their biocompatibility and intrinsic cell-specific interactions. This study describes the development of an EV-based nanocarrier system for cancer therapy using ultrasmall gold nanoclusters (1–2 nm) coated with a pH-sensitive PDPH linker connected to curcumin (AuNC–Cur–PDPH) through a hydrazone bond. The synthesized nanoclusters were characterized by means of morphology, optical properties, surface charge, and drug-loading efficiency using UV–visible spectroscopy, fluorescence spectroscopy, zeta potential analysis, transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). In order to maintain ADSC-derived EV bioactivities and nanocluster stability, AuNC–Cur–PDPH may be encapsulated into EVs by brief sonication (30 s) followed by incubation at room temperature. The successful loading and structural integrity were confirmed by dark-field microscopy, TEM, proteomic analysis, the Leprechaun exosome assay, and western blot analysis of EV markers. As compared to free curcumin, in A549 cancer cell in vitro studies, enhanced cellular uptake, improved retention, pH-controlled release of curcumin, and an increased apoptosis pathway rather than necrosis are expected when exposed to the 785 nm laser with 0.1 mW energy. The acid microenvironment of tumor cells helps the site-specific release of curcumin and helps to maintain the cellular homeostasis. Furthermore, the platform provides simultaneous photothermal and photodynamic therapy (PTT/PDT), offering a multimodal therapeutic approach. Surface-enhanced Raman spectroscopy (SERS) has been applied to trace EV internalization mechanisms and curcumin release kinetics at the single cellular level to understand molecular-level distribution mechanisms. Overall, the EV–AuNC–Cur–PDPH system represents a promising combined multifunctional nanocarrier for targeted cancer therapy and personalized medicine applications.
