Natural small molecule-polysaccharide nanoparticles: Preparation, characteristics-efficacy modulation, and drug delivery applications.

The rapid advancement of nanotechnology is revolutionizing fields like biology and materials science. However, concerns over the environmental and health impacts of conventional nanomaterials have spurred interest in sustainable alternatives. Natural small molecule-polysaccharide nanoparticles (NSM-PSNPs), synthesized from biocompatible and biodegradable polysaccharides and bioactive natural small molecules (NSMs), present a promising solution. These composite nanoparticles exhibit significant synergistic effects, enhancing the delivery, oral absorption, bioavailability, and controlled release of NSMs for therapeutic and other applications. Despite considerable progress, challenges remain in precisely controlling their structure-property relationships and understanding their behavior in complex biological environments. This review aims to address these challenges by providing strategic design principles for ideal NSM-PSNPs. It systematically outlines the classifications and properties of polysaccharides and NSMs, discusses assembly techniques for NSM-PSNPs, and analyzes the critical correlation between their characteristics and efficacy. Furthermore, the review examines key parameters affecting NSM-PSNPs properties to guide accurate control and explores their diverse applications, with a focus on drug delivery. Finally, it concludes by summarizing current challenges and future prospects in the development and application of NSM-PSNPs.