Low-liver-accumulation lipid nanoparticles enhance the efficacy and safety of HPV therapeutic tumor vaccines
Abstract Background Lipid nanoparticles (LNPs) hold significant potential in vaccine and cancer therapy, but conventional LNPs often cause hepatotoxicity and reduced efficacy due to liver accumulation. Methods LNP molecules with varying tail lengths were synthesized in vitro. Transfection efficiency...
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BMC
2025-08-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06924-2 |
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| author | Xiaodie Wang Zhidan Tian Meng Wang Xiaoru Cai Shuyan Yang Jianyao Zeng Yuan Fang Xuesen Bai Pei Wang Yan Sun Chuanxin Guo Tao Liu Qijun Qian |
| author_facet | Xiaodie Wang Zhidan Tian Meng Wang Xiaoru Cai Shuyan Yang Jianyao Zeng Yuan Fang Xuesen Bai Pei Wang Yan Sun Chuanxin Guo Tao Liu Qijun Qian |
| author_sort | Xiaodie Wang |
| collection | DOAJ |
| description | Abstract Background Lipid nanoparticles (LNPs) hold significant potential in vaccine and cancer therapy, but conventional LNPs often cause hepatotoxicity and reduced efficacy due to liver accumulation. Methods LNP molecules with varying tail lengths were synthesized in vitro. Transfection efficiency was assessed in vitro via flow cytometry. The BALB/c model was used to evaluate in vivo delivery efficiency of the LNPs. The C57BL/6 mouse model was used to evaluate in vivo anti-tumor pharmacodynamics, along with tumor-infiltrating immune cells and serum inflammatory cytokines. The Sprague Dawley (SD) rat model was used for toxicity testing of the candidate LNP. Results Lipid 7 demonstrated threefold higher mRNA expression efficiency at the injection site while minimizing liver retention. In an HPV tumor model, Lipid 7 achieved tumor suppression comparable to SM-102-based LNP but outperformed in remodeling the tumor microenvironment (dendritic cells: 12.1% vs. 5.1%; natural killer cells: 1.1% vs. 0.5%) and elevating serum immune cytokines (TNF-α, IL-1β, etc., 1.2–1.8-fold higher). Critically, Lipid 7 reduced off-target mRNA accumulation in the heart, liver, spleen, lungs, and kidneys, mitigating hepatotoxicity risks associated with traditional LNPs. Conclusions By employing a novel, non-patented ionizable lipid design, this work balances delivery efficiency and biosafety, Lipid 7 offers a high-efficacy, low-toxicity therapeutic strategy for HPV-related cancers. Graphical Abstract |
| format | Article |
| id | doaj-art-886e63a4aa5f43d7a4f20cfad59da7d8 |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-886e63a4aa5f43d7a4f20cfad59da7d82025-08-20T03:46:24ZengBMCJournal of Translational Medicine1479-58762025-08-0123111510.1186/s12967-025-06924-2Low-liver-accumulation lipid nanoparticles enhance the efficacy and safety of HPV therapeutic tumor vaccinesXiaodie Wang0Zhidan Tian1Meng Wang2Xiaoru Cai3Shuyan Yang4Jianyao Zeng5Yuan Fang6Xuesen Bai7Pei Wang8Yan Sun9Chuanxin Guo10Tao Liu11Qijun Qian12School of Medicine, Shanghai UniversityShanghai Cell Therapy Group Co., LtdShanghai Cell Therapy Group Co., LtdShanghai Cell Therapy Group Co., LtdShanghai Cell Therapy Group Co., LtdShanghai Cell Therapy Group Co., LtdSchool of Medicine, Shanghai UniversityShanghai Cell Therapy Group Co., LtdSchool of Medicine, Shanghai UniversitySchool of Medicine, Shanghai UniversityShanghai Cell Therapy Group Co., LtdShanghai Cell Therapy Group Co., LtdSchool of Medicine, Shanghai UniversityAbstract Background Lipid nanoparticles (LNPs) hold significant potential in vaccine and cancer therapy, but conventional LNPs often cause hepatotoxicity and reduced efficacy due to liver accumulation. Methods LNP molecules with varying tail lengths were synthesized in vitro. Transfection efficiency was assessed in vitro via flow cytometry. The BALB/c model was used to evaluate in vivo delivery efficiency of the LNPs. The C57BL/6 mouse model was used to evaluate in vivo anti-tumor pharmacodynamics, along with tumor-infiltrating immune cells and serum inflammatory cytokines. The Sprague Dawley (SD) rat model was used for toxicity testing of the candidate LNP. Results Lipid 7 demonstrated threefold higher mRNA expression efficiency at the injection site while minimizing liver retention. In an HPV tumor model, Lipid 7 achieved tumor suppression comparable to SM-102-based LNP but outperformed in remodeling the tumor microenvironment (dendritic cells: 12.1% vs. 5.1%; natural killer cells: 1.1% vs. 0.5%) and elevating serum immune cytokines (TNF-α, IL-1β, etc., 1.2–1.8-fold higher). Critically, Lipid 7 reduced off-target mRNA accumulation in the heart, liver, spleen, lungs, and kidneys, mitigating hepatotoxicity risks associated with traditional LNPs. Conclusions By employing a novel, non-patented ionizable lipid design, this work balances delivery efficiency and biosafety, Lipid 7 offers a high-efficacy, low-toxicity therapeutic strategy for HPV-related cancers. Graphical Abstracthttps://doi.org/10.1186/s12967-025-06924-2mRNA deliveryLipid nanoparticles (LNPs)Cancer immunotherapyHepatotoxicity mitigation |
| spellingShingle | Xiaodie Wang Zhidan Tian Meng Wang Xiaoru Cai Shuyan Yang Jianyao Zeng Yuan Fang Xuesen Bai Pei Wang Yan Sun Chuanxin Guo Tao Liu Qijun Qian Low-liver-accumulation lipid nanoparticles enhance the efficacy and safety of HPV therapeutic tumor vaccines Journal of Translational Medicine mRNA delivery Lipid nanoparticles (LNPs) Cancer immunotherapy Hepatotoxicity mitigation |
| title | Low-liver-accumulation lipid nanoparticles enhance the efficacy and safety of HPV therapeutic tumor vaccines |
| title_full | Low-liver-accumulation lipid nanoparticles enhance the efficacy and safety of HPV therapeutic tumor vaccines |
| title_fullStr | Low-liver-accumulation lipid nanoparticles enhance the efficacy and safety of HPV therapeutic tumor vaccines |
| title_full_unstemmed | Low-liver-accumulation lipid nanoparticles enhance the efficacy and safety of HPV therapeutic tumor vaccines |
| title_short | Low-liver-accumulation lipid nanoparticles enhance the efficacy and safety of HPV therapeutic tumor vaccines |
| title_sort | low liver accumulation lipid nanoparticles enhance the efficacy and safety of hpv therapeutic tumor vaccines |
| topic | mRNA delivery Lipid nanoparticles (LNPs) Cancer immunotherapy Hepatotoxicity mitigation |
| url | https://doi.org/10.1186/s12967-025-06924-2 |
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