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Screening Natural Cholesterol Analogs to Assemble Self-Adjuvant Lipid Nanoparticles for Antigens Tagging Guided
Shuang Liang1, Shuying Gao1, Shunli Fu1
1School of Pharmaceutical Sciences, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese, Qilu Hospital of Shandong University, The Second Hospital, Cheeloo College of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong, 250012, China.
Abstract:
The clinical progress of tumor nucleotide vaccines is limited due to insufficient recognition and killing of tumor cells with low antigen expression by cytotoxic T lymphocytes (CTL). Here, natural cholesterol analogs are screened to assemble self-adjuvant lipid nanoparticles (LNPs) for antigens tagging tumor cells and dendritic cells (DC) activation. First, a library of ginsenosides are collected, and then screened according to their anti-tumor immunity. Then, ginsenoside-Rg3 based-LNPs loaded with antigens (Rg3-LNPs) are identified as the optimal formulation by investigating the physicochemical and biological properties. Finally, Rg3-LNPs and granulocyte-macrophage colony-stimulating factor (GM-CSF) are co-loaded into a macroporous hydrogel for long-term immune response. Rg3-LNPs could accumulate into both tumors and LNs. Rg3-LNPs targeted tumor cells with high glucose transporter-1 expression via the targeting ligand Rg3, and anchored antigens on the tumor cell surface, thus promoting the recognition of CTL to tumor cells; Rg3-LNPs can accumulate into the LNs to promote DC activation and antigen presentation, thus stimulating CTL activation. Besides, Rg3, as an adjuvant, cooperated with GM-CSF to remodel the tumor microenvironment, thus promoting the killing of CTL to tumor cells. Collectively, this work highlights the importance of tagging antigens to tumor cells in tumor vaccine and has great clinical value for immune-escaping tumors.
Insights
This study developed novel lipid nanoparticles (LNPs) using ginsenosides to improve tumor vaccines. These Rg3-LNPs enhance tumor cell recognition and dendritic cell activation, boosting anti-tumor immunity for challenging cancers.
Area of Science:
- Immunology
- Nanotechnology
- Oncology
Background:
- Clinical efficacy of tumor nucleotide vaccines is hampered by poor tumor cell recognition and killing by cytotoxic T lymphocytes (CTLs), especially in tumors with low antigen expression.
- Developing effective cancer vaccines requires strategies to enhance antigen presentation and T cell responses against tumor cells.
Purpose of the Study:
- To screen natural cholesterol analogs for self-adjuvant lipid nanoparticles (LNPs) that can tag tumor cells and activate dendritic cells (DCs).
- To develop a novel LNP formulation for improved tumor vaccine efficacy against immune-evading tumors.
Main Methods:
- Screening a library of ginsenosides to identify compounds with anti-tumor immunity properties.
- Formulating ginsenoside-Rg3 based LNPs (Rg3-LNPs) loaded with antigens and evaluating their physicochemical and biological properties.
- Co-loading Rg3-LNPs and granulocyte-macrophage colony-stimulating factor (GM-CSF) into a macroporous hydrogel for sustained immune response.
Main Results:
- Ginsenoside-Rg3 based LNPs (Rg3-LNPs) were identified as the optimal formulation.
- Rg3-LNPs effectively accumulated in tumors and lymph nodes, targeting tumor cells with high glucose transporter-1 expression via Rg3.
- Rg3-LNPs promoted CTL recognition of tumor cells, enhanced DC activation and antigen presentation, and stimulated CTL activation, with Rg3 and GM-CSF remodeling the tumor microenvironment.
Conclusions:
- Tagging antigens to tumor cells using Rg3-LNPs is crucial for effective tumor vaccination.
- This novel approach holds significant clinical value for overcoming immune evasion in tumors and improving anti-tumor immune responses.
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