Gold Nanorods-Encapsulated Extracellular Vesicles: A Smart Approach to Cancer Therapy

The development of effective nanomedicine strategies for cancer therapy requires not only materials with suitable physicochemical and optical properties, but also a detailed understanding of their interactions with biological systems. This thesis investigates inorganic nanomaterials from two complementary perspectives: understanding nanoparticle–biomolecule interactions and developing a bioinspired platform for photothermal delivery. The first part of the work focuses on hydrothermal carbon nanoparticles (CNPs), a versatile class of carbon-based nanomaterials with tunable physicochemical properties and potential biomedical applications. Glucose-derived CNPs were synthesized by hydrothermal treatment and characterized in terms of size and surface properties. Their interaction with cytochrome c was investigated using complementary spectroscopic and analytical approaches, including UV–visible spectroscopy, ^1H NMR, circular dichroism, fluorescence, and electron paramagnetic resonance. The results demonstrated that CNPs can reduce cytochrome c, suppress its peroxidase activity, and induce persistent conformational changes in the protein. These effects were also investigated in the presence of a biomolecular corona, highlighting that nanoparticle surface reactivity can influence biomolecular redox processes and should be considered in the design of biomedical nanomaterials. The second part of the thesis focuses on the development of a hybrid gold nanorod (AuNR)–extracellular vesicle (EV) platform for photothermal therapy. AuNRs were synthesized and successfully surface-modified with a biocompatible surfactant to replace conventional surfactant stabilization and to improve their suitability for biological applications while preserving their near-infrared (NIR) optical and photothermal properties. The synthesised AuNRs retained their NIR absorption and demonstrated efficient heat generation under irradiation at 915 nm, confirming the preservation of their photothermal performance and functionality. The association and internalization of AuNRs within extracellular vesicles were subsequently investigated using two different approaches, including electroporation and extrusion. Among the strategies evaluated, extrusion enabled the successful incorporation of AuNRs into EVs, providing a promising approach for the preparation of EV–AuNRs hybrid systems while maintaining the potential of EVs as biomimetic carriers. The resulting EV–AuNRs platform combines the biological properties of extracellular vesicles with the NIR-responsive photothermal properties of gold nanorods, providing a basis for further investigation as a targeted photothermal nanomedicine platform. Overall, this thesis emphasizes the importance of integrating nanomaterial physicochemical properties, surface reactivity, and biological interactions in the development of biomedical nanoplatforms. The results contribute to a deeper understanding of carbon nanoparticle–protein interactions and demonstrate the successful surface engineering of AuNRs and their incorporation into extracellular vesicles by extrusion, providing a foundation for the development of biomimetic EV–AuNR systems for NIR-triggered photothermal therapy