Morphological Insights in Oxidative Sensitive Nanocarriers Pharmacokinetics, Targeting, and Photodynamic Therapy

Abstract

The examination of nanoparticle morphology holds significant importance within the field of nanomedicine, particularly concerning its implications for biological responses. This study investigates the impact of synthesizing polymers with varying degrees of methionine (MET) polymerization on three distinct drug delivery systems: spherical micelles, worm-like micelles, and vesicles. These systems were loaded with the photosensitizer Chlorin e6 (Ce6), and their distribution was meticulously analyzed at both cellular and animal levels. Our findings reveal insights into how nanoparticle morphology influences crucial aspects such as cellular uptake, subcellular localization, penetration of multicellular spheroids, blood half-life, and biodistributions across major organs. Employing a physiologically based pharmacokinetic (PBPK) model enabled us to simulate diverse distribution patterns and quantify the targeting efficiency of nanoparticles toward tumors. Our investigation elucidates that spherical micelles exhibit lower accumulation levels within the reticuloendothelial system (RES), potentially mitigating adverse side effects despite their higher glomerular filtration rate. This nuanced understanding underscores the complex interplay between nanoparticle morphology and biological responses, providing valuable insights into optimizing therapeutic efficacy while minimizing undesirable effects. We thus report the integration of experimental analyses with PBPK modeling to elucidate the topological characteristics of nanoparticles, thereby shedding light on their distribution patterns, therapeutic efficacy, and potential side effects.