Screening Natural Cholesterol Analogs to Assemble Self‐Adjuvant Lipid Nanoparticles for Antigens Tagging Guided Therapeutic Tumor Vaccine
Abstract
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.
Article Details
Authors (10)
Shuang Liang
State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry
Shuying Gao
School 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
Shunli Fu
School 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
Shijun Yuan
Jinhu Liu
School 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
Man Liang
State Key Laboratory of Tropic Ocean Engineering Materials and Materials Evaluation School of Chemistry and Chemical Engineering Hainan University Haikou China
Leiqiang Han
School 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
Zipeng Zhang
State Key Laboratory of Synergistic Chem-Bio Synthesis, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering, Zhangjiang Institute for Advanced Study
Yongjun Liu
State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules, Zhangjiang Institute for Advanced Study and National Center for Translational Medicine
Na Zhang
High Magnetic Field Laboratory, Hefei Institutes of Physical Science