Novel doxycycline gold nanoparticles <i>via</i> green synthesis using PEO-PPO block copolymers for enhanced radiosensitization of melanoma

This study focuses on a green and sustainable nanoplatform for the delivery of therapeutic agents, based on gold nanoparticles (AuNPs) synthesized using PEO-PPO block copolymers (F127, F68, P85, and their F127:P85 combination) as dual-function reducing and stabilizing agents. This eco-friendly approach eliminates the need for toxic chemical reductants, adheres to green chemistry principles, and yields highly stable, biocompatible nanosystems. The resulting polymer-stabilized AuNPs were associated with doxycycline (DOXY), a mitochondrial biogenesis inhibitor with radiosensitizing properties, and characterized using UV-Vis spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), and X-ray fluorescence (XRF). The nanoparticles exhibited high colloidal stability, with tunable hydrodynamic diameters modulated by the copolymer composition. <i>In vitro</i> studies on A-375 and IIB-MEL-J melanoma cell lines revealed that DOXY-associated AuNPs, combined with gamma radiation (2 Gy, 137Cs), significantly enhanced radiosensitivity, reducing both cell viability and clonogenic survival. The physicochemical features of the nanosystems, particularly particle size and surface composition, influenced cellular uptake and therapeutic response. Notably, AuNPs stabilized with F127:P85 copolymer combination (∼19 nm) outperformed those with F127 (∼30 nm), despite displaying slightly higher polydispersity. Compared to Turkevich AuNPs, our copolymer-coated nanosystems demonstrated superior colloidal stability and cellular internalization. These findings highlight the potential of green-synthesized AuNPs as multifunctional, biocompatible platforms for therapeutic delivery, supporting the development of effective and environmentally responsible multimodal cancer therapies. Moreover, the simplicity, scalability, and cost-effectiveness of the synthesis process support its potential for future translational applications.