Photothermal Transport for Guiding Nanoparticles Through the Vitreous Humor

Visual impairments affect over 2.2 billion people worldwide, yet delivering drugs to the posterior segment of the eye, including the retina, remains a major challenge. Intravitreal injection, the standard administration route, often results in suboptimal drug diffusion through the vitreous, limiting drug access to the retina. While various strategies have been explored to enhance the mobility of drug molecules and nanomedicines (drugs encapsulated in nanoparticles) in the vitreous, no method has demonstrated guided transport. Here, we investigate photothermal transport of nanoparticles in the vitreous using a pulsed laser and indocyanine green, both clinically approved modalities. We show that photothermal transport guides nanoparticles from one location in the vitreous toward the laser-illuminated area, away from the injection spot. Multiple-particle tracking and numerical simulations reveal that this motion is predominantly driven by thermal convection, with thermophoresis contributing to a lesser extent. We identified parameters for optimization, including dye concentration, particle size, distance from the laser focus, and laser fluence. These findings establish a novel and clinically relevant paradigm for light-guided drug delivery in the eye. To our knowledge, this is the first demonstration of guided light-controlled particle transport in the vitreous using ocular dyes and pulsed lasers routinely applied in ophthalmology.