The evolution of polysaccharides in modulating tumor immune cells: From immunoactive molecules to nanoparticles.

Immunoactive polysaccharides can interact with pattern recognition receptors (PRRs) to activate innate immune components such as dendritic cells (DCs), macrophages, and natural killer (NK) cells. Nevertheless, their large molecular weight and complex structure lead to instability in their immune activity, limiting their clinical application in tumor immunotherapy. Nanotechnology offers a solution to enhance the antitumor effects of polysaccharides. The combination of polysaccharides with other components in nanoparticles has been widely discussed in terms of drug loading, delivery precision, and immune activation. However, few studies have explored how the behavior of immunologically active polysaccharides in nanoparticles and their interactions with other components impact antitumor activity. This review aims to systematically elucidate the mechanisms of interaction between polysaccharides and other components, and explore their impact on antitumor activity following nanoparticle formulation. We focus on analyzing the interactions between immunologically active polysaccharides and other components within polysaccharide-based nanoparticles, to clarify the potential mechanisms that enhance antitumor efficacy. Additionally, we discuss the clinical translation prospects and challenges of these nanoparticle systems and propose strategies to address them. This work provides a theoretical foundation for the design and development of multifunctional, immunomodulatory polysaccharide-based nanoparticles, offering valuable insights for their clinical translation.