PEGylating Ag2S Semiconductor Nanocrystals for Pharmacokinetics Tracking: Insights from NIR Luminescence Imaging

Abstract

Nanotechnology has revolutionized biomedical applications through the development of nanomaterials with tailored properties, particularly in disease diagnosis and treatment. However, challenges remain regarding the pharmacokinetics of nanomaterials, which influence their biodistribution, targeting efficiency, clearance, and potential toxicity. Nearinfrared (NIR) imaging has emerged as a promising tool to study the in vivo behavior of nanomaterials, offering noninvasive, real-time analysis of drug delivery and nanocarrier distribution. Despite its potential, the lack of robust analytical models for precise biodistribution and excretion measurements limits its clinical translation. This study investigates the biodistribution and pharmacokinetics of fluorescent Ag2S nanoparticles (NPs) with varying surface charges and capping agent size. These NPs, emitting light at ∼1200 nm in the NIR-II biological window, allow real-time tracking of their distribution. We explored the effects of polyethylene glycol functionalization with different molecular weights on NP behavior. A novel analytical model was developed to assess pharmacokinetic parameters and the influence of surface chemistry on protein−NP interactions. In vitro experiments confirmed that protein binding alters the surface charge and colloidal properties of NPs, which impacts their pharmacokinetics. This work advances our understanding of how nanoparticle surface modifications affect their in vivo performance and interactions with biological systems.