Glucan-Based Nanoparticles Empower Precision Cancer Immunotherapy: Design Strategies, Immune Reprogramming Mechanisms, and Clinical Translation Prospects

Tumor immunotherapy presents new opportunities for sustained tumor control by reinstating immune surveillance. However, its clinical efficacy is significantly limited by the immunosuppressive nature of the tumor microenvironment, considerable variability in patient responses, and the delicate balance required between immune activation and systemic toxicity. Recently, glucan-based nanoparticles have gained prominence as engineered platforms in precision tumor immunotherapy due to their favorable biocompatibility, programmable structural design, and inherent immune recognition capabilities. Comprehensive research has shown that these nanosystems not only facilitate the precise delivery of tumor antigens, immunoadjuvants, and immunomodulatory agents but also modulate the tumor immune microenvironment at various levels. These nanoparticles specifically target antigen-presenting cells, reprogram tumor-associated macrophages’ phenotypes, reduce the function of immunosuppressive cells, and synergistically activate both innate and adaptive immune responses, significantly boosting antitumor immunity. This review methodically examines the principal strategies in the structural design and surface functionalization of glucan-based nanoparticles, with a focus on the molecular and cellular mechanisms of immune remodeling. It further highlights recent progress in their combined use with various immunotherapeutic modalities, such as immune checkpoint inhibitors, photodynamic or photothermal therapies, and cell-based treatments. Moreover, drawing on current preclinical studies and early clinical data, this article offers a comprehensive evaluation of the translational challenges these systems face, including long-term safety, scalable production, and regulatory issues. Overall, glucan-based nanoparticles are transitioning from traditional delivery systems to versatile therapeutic platforms that play a crucial role in immune regulation. They offer significant potential for novel theoretical frameworks and technological advances in the development of more precise, effective, and sustainable tumor immunotherapy strategies. The infographic illustrates the construction, mechanism and application of glucan-based nanoparticles. In the construction section, it highlights regulation of physicochemical properties such as size, charge and functional modification loading. It also mentions intelligent responsive design and acid environment adaptation. The mechanism section shows enhancement of antigen delivery and presentation, reshaping the immunosuppressive microenvironment and CD8 superscript plus T cell activation. The application section covers biocompatibility and safety, production process and quality control and clinical trial design. It also includes tumor vaccine delivery system, immune checkpoint blockade therapy and combination therapy strategy involving immunotherapy, chemotherapy and PTT.Infographic on glucan-based nanoparticles: construction, mechanism and application in cancer therapy.