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Guo, Zhen, Xian, Peng, Green, Donovan, Hu, Kai-Li and Yin, Lei-Miao (2025) Nanosized natural products for immune dysregulation: a systematic review of mechanisms, therapeutic applications, and translational challenges. Phytomedicine (157582). pp. 1-70. ISSN 0944-7113
Background:
Natural products possess remarkable bidirectional immunomodulatory properties, offering great promise for treating diseases characterized by immune dysregulation, such as cancer and inflammation. However, poor solubility, accelerated metabolism, and the lack of tissue specificity hinder their clinical translation. Nanotechnology has emerged as a powerful strategy to overcome these intrinsic limitations, enhancing the bioavailability and therapeutic potential of natural products.
Purpose:
To evaluate how nanosized natural products overcome these barriers to enhance the immunoregulatory efficacy of natural products. Also to summarise their mechanisms and therapeutic advantages with a view to elaborating on future translational challenges.
Methods:
All the relevant clinical and research studies conducted on the application and efficacy of nanosized natural products in immune dysregulation diseases were included, as retrieved from PubMed, Web of Science, ScienceDirect, and Google Scholar, following the use of specific search terms.
Results:
This review systematically evaluates important advancements in nanosized natural products-based immunomodulators, including nano drugs and vaccine adjuvants. By integrating evidence from in vitro, in vivo, and clinical studies, we highlight how nanosized natural products protect biologically active substance, prolong immune responses, enable targeted delivery, and alleviate toxic side effects. We have discussed the mechanisms by which these nanosized natural products modulate key immunosuppressive components, including T lymphocytes, dendritic cells, macrophages, natural killer cells, and neutrophils, to restore equilibrium to homeostasis. The use of nanosized natural products in the enhancement of cancer immunotherapy and their ameloriaton of concomitant inflammatory diseases is also discussed extensively.
Conclusion:
Nanosized natural products represent a transformative approach for precise immunomodulation. They bridge the gap between the therapeutic potential of natural compounds and clinical application. Future success hinges on addressing challenges in scalable manufacturing, long-term toxicology, and designing smarter stimuli-responsive delivery systems.
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