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<p>In colorectal cancer, the cancer-immunity cycle is often disrupted by the lack of effective tumor-associated antigens, impaired activation of antigen-presenting cells, and insufficient T cell infiltration, leading to tumor immune escape and disease progression. Therefore, we developed PTX-GLSO SEDDS@GLS (PGS@GLS), a multicomponent solid self-emulsifying drug delivery system (SEDDS) incorporating paclitaxel (PTX) and <i>Ganoderma lucidum</i> spore oil (GLSO), with processed <i>Ganoderma lucidum</i> spores (GLS) as the solid carrier. The intestinal lymphatic absorption of PTX-GLSO SEDDS was significantly enhanced after GLS solidification, facilitating the induction of immune responses. Additionally, the oil phase of GLSO enhanced PTX solubility through self-emulsification into nanoemulsion. In tumors and the mesenteric lymphatic system, PGS@GLS induced robust immunogenic cell death and triggered the release of damage-associated molecular patterns, thereby initiating the cancer-immunity cycle. Furthermore, GLSO and GLS synergistically promoted dendritic cell maturation and cytotoxic T cell activation, thereby potentiating anti-tumor immune responses. Tumor cells were killed by the accumulated cytotoxic T cells, and the resulting dead tumor cells released additional tumor-associated antigens, which were subsequently presented by dendritic cells, creating a positive feedback loop to amplify the cancer-immunity cycle. Notably, PGS@GLS maintained potent antitumor efficacy while mitigated PTX-related systemic toxicity, representing a promising oral chemoimmunotherapy platform that restores antitumor immunity through lymphatic transport-mediated cancer-immunity cycle reinforcement.</p> Graphical Abstract <p></p>

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Multicomponent Ganoderma lucidum spore-based solid self-nanoemulsifying system of paclitaxel for improved lymphatic absorption and immune synergistic antitumor strategy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月23日

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  • Wenyou Fang,
  • Mingchao Xu,
  • Huiru Li,
  • Lujun Wang,
  • Wenjie Lu,
  • Xia Liu,
  • Shengqi Chen,
  • Song Gao,
  • Qing Zhang,
  • Rongfeng Hu

摘要

In colorectal cancer, the cancer-immunity cycle is often disrupted by the lack of effective tumor-associated antigens, impaired activation of antigen-presenting cells, and insufficient T cell infiltration, leading to tumor immune escape and disease progression. Therefore, we developed PTX-GLSO SEDDS@GLS (PGS@GLS), a multicomponent solid self-emulsifying drug delivery system (SEDDS) incorporating paclitaxel (PTX) and Ganoderma lucidum spore oil (GLSO), with processed Ganoderma lucidum spores (GLS) as the solid carrier. The intestinal lymphatic absorption of PTX-GLSO SEDDS was significantly enhanced after GLS solidification, facilitating the induction of immune responses. Additionally, the oil phase of GLSO enhanced PTX solubility through self-emulsification into nanoemulsion. In tumors and the mesenteric lymphatic system, PGS@GLS induced robust immunogenic cell death and triggered the release of damage-associated molecular patterns, thereby initiating the cancer-immunity cycle. Furthermore, GLSO and GLS synergistically promoted dendritic cell maturation and cytotoxic T cell activation, thereby potentiating anti-tumor immune responses. Tumor cells were killed by the accumulated cytotoxic T cells, and the resulting dead tumor cells released additional tumor-associated antigens, which were subsequently presented by dendritic cells, creating a positive feedback loop to amplify the cancer-immunity cycle. Notably, PGS@GLS maintained potent antitumor efficacy while mitigated PTX-related systemic toxicity, representing a promising oral chemoimmunotherapy platform that restores antitumor immunity through lymphatic transport-mediated cancer-immunity cycle reinforcement.

Graphical Abstract