Medicinal Plant Research 2024, Vol.14, No.6, 358-370 http://hortherbpublisher.com/index.php/mpr 358 Research Insight Open Access Chemical Modification of Cordyceps Polysaccharides and Their Antitumor Activity Baofu Huang1, Jianhui Li 2 1 Traditional Chinese Medicine Research Center, Cuixi Academy of Biotechnology, Zhuji, 311800, China 2 Institute of Life Sciences, Jiyang Colloge of Zhejiang A&F University, Zhuji, 311800, Zhejiang, China Corresponding author: jianhui.li@jicat.org Medicinal Plant Research, 2024, Vol.14, No.6 doi: 10.5376/mpr.2024.14.0030 Received: 06 Nov., 2024 Accepted: 15 Dec., 2024 Published: 30 Dec., 2024 Copyright © 2024 Huang and Li, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Huang B.F., and Li J.H., 2024, Chemical modification of Cordyceps polysaccharides and their antitumor activity, Medicinal Plant Research, 14(6): 358-370 (doi: 10.5376/mpr.2024.14.0030) Abstract Cordyceps polysaccharides have been frequently mentioned in functional foods and cancer adjuvant therapy in recent years because of their immunomodulatory and anti-tumor activities. However, there are also many problems, such as poor water solubility and low bioavailability, which affect the actual application effect. This study systematically explored various chemical modification methods of Cordyceps polysaccharides (e.g., sulfonation, phosphorylation, selenization, acetylation and nanocarrier grafting), and analyzed the effects of these structural modifications on their anti-tumor activity. The results showed that as long as the modification is appropriate, such as the introduction of functional groups at specific sites, it can not only enhance its ability to induce apoptosis and immune activation, but also help improve tumor targeting and safety. In animal models, a variety of modified polysaccharides showed obvious tumor inhibition effects. In addition, we also discussed its potential as an anti-tumor drug candidate in combination with structure-activity analysis and several typical cases. Of course, from experiments to industry, there are still challenges such as production stability and clinical transformation. This study provides support for the integration of Cordyceps polysaccharides into combined treatment strategies and nano-delivery systems. Keywords Cordyceps polysaccharide; Chemical modification; Antitumor activity; Structure-activity relationship; Immunomodulation; Nanodrug delivery 1 Introduction Cordyceps, like Cordyceps sinensis and Cordyceps militaris, have been used in traditional Asian medicine for hundreds of years. People value them for many health benefits, such as boosting the immune system, reducing inflammation, and fighting tumors (Zhang et al., 2019; Jędrejko et al., 2021; Liu et al., 2022). One of the main helpful parts in Cordyceps is its polysaccharides. These sugars seem to play a big role in health effects. They can help the body by turning on immune cells, making cancer cells die, and changing the tumor environment to slow down its growth (Bi et al., 2018; 2020; Qi et al., 2020). Because of these effects, Cordyceps polysaccharides are now being added to health foods and are also being looked at as possible support drugs in cancer treatment (Zhang et al., 2019; Miao et al., 2022; Chatnarin and Thirabunyanon, 2023). Cordyceps polysaccharides come in many forms. They can be very different in size, sugar types (like glucose, mannose, or galactose), how the sugars are linked, and how the chains are branched (Jing et al., 2014; Miao et al., 2022; Dai et al., 2024b; Zhu et al., 2024; Li et al., 2025). These differences in structure matter a lot. They can change how well the polysaccharides boost the immune system, kill cancer cells, or stop tumors from growing (Jing et al., 2015; Miao et al., 2022). In recent years, better lab tools have made it easier for scientists to study these structures in more detail. This has helped them understand how the shape of a polysaccharide is linked to what it can do—especially in fighting cancer (Miao et al., 2022; Zhao et al., 2023). Although Cordyceps polysaccharides exhibit good biological activity, their application in clinical tumor treatment still faces many limitations, mainly manifested in large molecular weight, poor water solubility and low bioavailability (Xie et al., 2020; Zhu et al., 2024). These factors affect its absorption, distribution and ability to target tumor tissues in the body, reducing its actual therapeutic potential (Xie et al., 2020; Zhu et al., 2024).
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