Morphological Features Influence the Drug Loading and Delivery Efficacy of Photoactivatable Gold Nanocarriers for Antitumor Photo/Chemotherapy

Photoactivatable gold nanocarriers are transforming antitumor therapies by leveraging their distinctive physicochemical properties, enabling targeted drug delivery and enhanced therapeutic efficacy in cancer treatment. This study systematically investigates how surface topography and morphology of gold nanocarriers influence drug loading capacity, light-to-heat conversion efficiency, and overall therapeutic performance in photo/chemotherapy. We synthesized four distinct morphologies of gold nanoparticles: porous gold nanocups (PAuNCs), porous gold nanospheres (PAuNSs), solid gold nanocups (SAuNCs), and solid gold nanospheres (SAuNSs). By examining these morphologies, we isolated the effects of surface roughness, porosity, and inner cavity structures on the critical therapeutic parameters. Our findings reveal that PAuNCs exhibit superior drug loading capabilities due to their enhanced surface area and porosity, facilitating greater interaction with therapeutic agents. Whereas, dissolution kinetic modeling confirmed that porosity contributes to improve diffusion-controlled drug release. <i>In vitro</i> studies on HepG2 cancer cells demonstrated that PAuNCs markedly improved cellular uptake, resulting in a dramatic reduction in cell viability to 3% and a notable increase in apoptosis (60.45%). Under near-infrared (NIR) irradiation, PAuNCs effectively induced localized hyperthermia (46.7 °C) and significantly inhibited tumor growth in an <i>in vivo</i> HepG2 tumor mice model compared with alternative nanogold morphologies. This research underscores the critical role of surface roughness, porosity, morphology, and cavitation in optimizing drug delivery and enhancing therapeutic outcomes of photoactivatable gold nanocarriers for collaborative photochemotherapy.