Medicinal Plant Research 2024, Vol.14, No.6, 358-370 http://hortherbpublisher.com/index.php/mpr 364 5.3 Pharmacokinetic properties and biodistribution If the therapeutic effects of modified Cordyceps polysaccharides are noteworthy, their performance in vivo cannot be ignored. In particular, with the help of nanotechnology, such as acetic acid-modified Cordyceps polysaccharide nanoparticles and selenium nanocomplexes, these new forms have shown obvious pharmacokinetic advantages (Guan et al., 2020; Qi et al., 2020; Wang et al., 2024). The drug is not only released more slowly and more stable in the body, but also stays in the blood longer, which is helpful for reducing the frequency of dosing and extending the efficacy window, making it more suitable for clinical use. More importantly, these modified nanocarriers have another advantage - they are easier to aggregate in tumor tissues. In animal experiments, nanoparticles showed good targeting ability, which not only improved the utilization rate of active ingredients, but also reduced systemic toxicity (Qi et al., 2020; Chen et al., 2024; Wang et al., 2024). In other words, the drug cures the disease while causing less damage to normal tissues. Other studies have attempted to use black phosphorus nanosheets to carry cordyceps polysaccharides to build a more targeted delivery system. This system can not only achieve tumor localization, but also adapt to the needs of photothermal therapy, and even show a certain synergistic effect in activating immune responses (Wang et al., 2024). This type of combined strategy shows that Cordyceps polysaccharides are not only auxiliary, but can also play a more core role in modern anti-tumor treatment. 6 Mechanisms of Antitumor Action of Cordyceps Polysaccharides 6.1 Immune activation pathways induced by Cordyceps polysaccharides Cordyceps polysaccharides can strongly activate the innate immune system, especially by activating macrophages and natural killer cells (NK cells) to exert anti-tumor effects. These polysaccharides not only enhance the phagocytic activity of macrophages, but also induce tumor-associated macrophages (TAMs) to transform from the immunosuppressive M2 phenotype to the cytotoxic M1 phenotype, and enhance the cytotoxic ability of NK cells against tumor cells (Bi et al., 2020; Wan et al., 2023; Wang et al., 2024). Mechanistically, this immune activation is mediated by the recognition of pattern recognition receptors (such as TLR2 and Dectin-1), activating downstream signaling pathways such as p38, Akt, NF-κB and Syk, thereby enhancing the activity of immune cells and promoting tumor cell clearance (Bi et al., 2020; Wan et al., 2023). Animal experiments have confirmed that these immune effects can effectively inhibit tumor growth and have better safety than traditional chemotherapy drugs (Bi et al., 2020; Wang et al., 2024). Cordyceps polysaccharides also modulate the tumor microenvironment by enhancing the secretion of key cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), interleukin-6 (IL-6), and interferon-gamma (IFN-γ) (Dai et al., 2024a; Li et al., 2025). This cytokine upregulation boosts both innate and adaptive immune responses, promoting T cell proliferation, dendritic cell maturation, and overall antitumor immunity (Li et al., 2025). The increased cytokine milieu not only supports direct tumor cell killing but also helps reset immune cell phenotypes, overcoming tumor-induced immunosuppression (Liu et al., 2022; Deng et al., 2022; Wan et al., 2023; Zhu et al., 2024). Cordyceps polysaccharides further modulate the tumor microenvironment by promoting the secretion of key cytokines such as TNF-α, IL-2, IL-6, and IFN-γ (Dai et al., 2024a; Li et al., 2025). The upregulation of these cytokines can enhance innate and adaptive immune responses, promote T cell proliferation, and dendritic cell maturation, thereby enhancing overall anti-tumor immunity (Li et al., 2025). Increased cytokine levels not only help to directly eliminate tumor cells, but also reshape the phenotype of immune cells, thereby reversing the tumor-induced immunosuppressive state (Liu et al., 2022; Deng et al., 2022; Wan et al., 2023; Zhu et al., 2024). 6.2 Apoptotic and anti-proliferative mechanisms One of the core mechanisms by which Cordyceps polysaccharides exert their anti-tumor effects is to induce apoptosis by activating the caspase pathway. These polysaccharides can upregulate pro-apoptotic proteins (such as Bax and p53), promote the release of cytochrome c from mitochondria, and activate caspase-3, -8, and -9, thereby inducing programmed cell death in a variety of tumor cell lines (Cui et al., 2018; Liu et al., 2019; Jo et al., 2020;
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