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Multicomponent Ganoderma lucidum spore-based solid self-nanoemulsifying system of paclitaxel for improved lymphatic
Wenyou Fang1, Mingchao Xu1, Huiru Li1
1School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230038, Anhui, China.
Abstract:
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.
Insights
A novel oral drug delivery system, PGS@GLS, enhances colorectal cancer treatment by boosting the cancer-immunity cycle. It improves drug absorption and immune cell activation, leading to potent anti-tumor effects with reduced toxicity.
Area of Science:
- Oncology
- Immunology
- Drug Delivery Systems
Background:
- Colorectal cancer (CRC) progression is linked to a disrupted cancer-immunity cycle.
- Key disruptions include lack of tumor antigens, impaired antigen-presenting cells, and poor T cell infiltration, leading to immune escape.
Purpose of the Study:
- To develop and evaluate a novel oral chemoimmunotherapy platform, PTX-GLSO SEDDS@GLS (PGS@GLS), for colorectal cancer.
- To investigate PGS@GLS's ability to restore the cancer-immunity cycle via enhanced lymphatic transport and immune cell activation.
Main Methods:
- Development of a solid self-emulsifying drug delivery system (SEDDS) encapsulating paclitaxel (PTX) and Ganoderma lucidum spore oil (GLSO) on a processed Ganoderma lucidum spores (GLS) carrier.
- Assessment of lymphatic absorption, induction of immunogenic cell death, release of damage-associated molecular patterns, and activation of dendritic cells and cytotoxic T cells.
- Evaluation of anti-tumor efficacy and systemic toxicity in a colorectal cancer model.
Main Results:
- GLS solidification significantly enhanced intestinal lymphatic absorption of PTX-GLSO SEDDS.
- PGS@GLS induced robust immunogenic cell death and initiated the cancer-immunity cycle in tumors and the lymphatic system.
- GLSO and GLS synergistically promoted dendritic cell maturation and cytotoxic T cell activation, leading to potent anti-tumor immune responses and reduced PTX toxicity.
Conclusions:
- PGS@GLS effectively restores the cancer-immunity cycle through lymphatic transport-mediated reinforcement.
- This oral chemoimmunotherapy platform demonstrates potent anti-tumor efficacy while mitigating systemic toxicity.
- PGS@GLS represents a promising strategy for enhancing colorectal cancer treatment by reactivating anti-tumor immunity.
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