Advances in Lipid Nanoparticle Carriers for Cancer Therapy
DOI:
https://doi.org/10.54097/ba1k0z68Keywords:
Lipid Nanoparticles, mRNA Vaccines, Cancer Gene TherapyAbstract
Malignant tumors, featuring strong heterogeneity, innate immune escape and acquired drug resistance, is the top cause of disease-related death worldwide. Traditional treatments for these cancers have serious drawbacks in terms of therapeutic efficacy and safety. Lipid nanoparticle (LNP) is the most powerful nonviral nucleic acid delivery vector to date and can achieve efficient encapsulation, protection and intracellular delivery of nucleic acid molecules with a biomimetic nanostructure interlinked synergistically assembled by core components, has become a key research vehicle in the field of cancer gene therapy. In this review, we summarize the composition of core functions of the component of LNPs, molecular evolution trajectory, targeting optimization and so on, and system summarize the latest research progress of LNP in targeted delivery of traditional chemotherapeutic agents, specific gene regulation by nucleic acid therapy and combination cancer therapy etc. Collectively, these pieces of work provide a complete academic reference for future fundamental studies and clinical translation of LNP-mediated cancer gene therapy technologies, and lay the theoretical basis for further non-viral nucleic acid vectors used in cancer gene therapy in the wider biomedical field.
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[1] Mendes, B. B., Conniot, J., Avital, A., Yao, D., Jiang, X., & Zhou, X. (2022). Nanodelivery of nucleic acids. Nature Reviews Methods Primers, 2, 24. https://doi. org/10. 1038/ s435 86-022-00024-7.
[2] Su, K., Shi, L., Sheng, T., Yan, X., Lin, L., Meng, C., ... & Liu, S. (2024). Reformulating lipid nanoparticles for organ-targeted mRNA accumulation and translation. Nature Communications, 15, 5659. https://doi.org/10.1038/s41467-024-49862-1.
[3] Sarnelli, S., Cardamone, M., Reverchon, E., & Baldino, L. (2025). Lipid-based nanoparticles for nucleic acids delivery. Physical Sciences Reviews, 10(3), 317–338. https://doi.org/ 10. 1515/ psr-2024-0046.
[4] Biscans, A., Ly, S., McHugh, N., Cooper, D. A., & Khvorova, A. (2022). Engineered ionizable lipid siRNA conjugates enhance endosomal escape but induce toxicity in vivo. Journal of Controlled Release, 349, 831–843. https://doi.org/10. 1016/ j. jconrel.2022.07.044.
[5] Yu, H., Dyett, B. P., Drummond, C. J., & Zhai, J. (2025). Ionizable lipid nanoparticles for mRNA delivery: Internal self-assembled inverse mesophase structure and endosomal escape. Accounts of Chemical Research, 58(20), 3210–3222. https:// doi. org/10.1021/acs.accounts.5c00412.
[6] Kong, W., Wei, Y., Dong, Z., Liu, W., Zhao, J., Huang, Y., Yang, J., Wu, W., He, H., & Qi, J. (2024). Role of size, surface charge, and PEGylated lipids of lipid nanoparticles (LNPs) on intramuscular delivery of mRNA. Journal of Nanobiotechnology, 22, 553. https://doi.org/10.1186/s12951-024-02653-9.
[7] Nosova, A. S., Koloskova, O. O., Nikonova, A. A., Simonova, V. A., Smirnov, V. V., Kudlay, D., & Khaitov, M. R. (2019). Diversity of PEGylation methods of liposomes and their influence on RNA delivery. MedChemComm, 10, 369–377. https://doi.org/10.1039/C8MD00780A.
[8] Patel, P., Fetse, J., Lin, C. Y., Guo, Y., Hasan, M. R., Nakhjiri, M., Zhao, Z., Jain, A., & Cheng, K. (2022). Development of amino acid-modified biodegradable lipid nanoparticles for siRNA delivery. Acta Biomaterialia, 154, 374–384. https:// doi. org/ 10.1016/j.actbio.2022.10.015.
[9] Chen, J., Ye, Z., Huang, C., Qiu, M., Song, D., Li, Y., & Xu, Q. (2022). Lipid nanoparticle-mediated lymph node-targeting delivery of mRNA cancer vaccine elicits robust CD8+ T cell response. Proceedings of the National Academy of Sciences of the United States of America, 119(34), e2207841119. https:// doi. org/10.1073/pnas.2207841119.
[10] Tan, J., Fang, J., Luo, W., Chen, X., Liang, Y., Huang, Z., Tan, S., Ren, M., Xu, X., Zhang, W., & Saw, P. E. (2025). Co-delivery of chemotherapy and anti-angiogenic lipid via DPPA-LNPs potentiates anti-PD-1 immunotherapy. International Journal of Nanomedicine, 20, 14057–14073. https://doi.org/ 10. 2147/IJN. S463217.
[11] Rajana, N., Chary, P. S., Bhavana, V., Deshmukh, R., Dukka, K., Sharma, A., & Mehra, N. K. (2024). Targeted delivery and apoptosis induction of CDK-4/6 inhibitor loaded folic acid decorated lipid-polymer hybrid nanoparticles in breast cancer cells. International Journal of Pharmaceutics, 651, 123787. https://doi.org/10.1016/j.ijpharm.2024.123787.
[12] Djermane, R., Nieto, C., Vega, M. A., & del Valle, E. M. M. (2024). EGFR-targeting polydopamine nanoparticles co-loaded with 5-fluorouracil, irinotecan, and leucovorin to potentially enhance metastatic colorectal cancer therapy. Scientific Reports, 14(1), 29265. https://doi.org/ 10.1038/ s41 598-024-79921-2.
[13] Quick, J., Dos Santos, N., Cheng, M. H. Y., Chander, N., Ghaemi, B., Chien, C. L., & Cullis, P. R. (2022). Lipid nanoparticles to silence androgen receptor variants for prostate cancer therapy. Journal of Controlled Release, 349, 174–183. https://doi.org/10.1016/j.jconrel.2022.07.031.
[14] Bao, M., Ehexige, E., Bazarjav, P., Yu, X., Damba, T., Zhang, Y., & Baigude, H. (2020). Silencing of STAT3 via peptidomimetic LNP-mediated systemic delivery of RNAi downregulates PD-L1 and inhibits melanoma growth. Biomolecules, 10(2), 285. https://doi.org/10.3390/ biom 1002 0285.
[15] Bai, L., Hao, X., Xu, W., Huang, H., Guo, M., Zhang, Y., Xiang, D., Yang, G., Wu, J., & Chen, C. (2025). FMRP silencing via siRNA lipid nanoparticles to reprogram the tumor microenvironment and enhance anti-PD-1 efficacy in triple-negative breast cancer. Materials Today Bio, 33, 102075. https://doi.org/10.1016/j.mtbio.2025.102075.
[16] Liu, S., Wei, L. X., Yu, Q., Guo, Z. W., Zhan, C. Y., Chen, L. L., Li, Y., & Ye, D. (2025). Targeting IRG1 in tumor-associated macrophages for cancer therapy. Protein & Cell, 16(6), 478–483. https://doi.org/10.1093/procel/pvae019.
[17] Broderick, J. C., Adams, A. M., Barbera, E. L., Van Decar, S., Clifton, G. T., & Peoples, G. E. (2025). Melanoma vaccines: Comparing novel adjuvant treatments in high-risk patients. Vaccines, 13(6), 656. https://doi.org/10.3390/ vaccines 130 60656.
[18] Liu, C., Zhang, K., Ge, R., Wang, W., Liu, X., Li, X., Hao, P., & Li, H. (2026). Boosting mRNA therapeutics: pHLIP enhances endosomal escape and gene expression in lipid nanoparticle. Advanced Healthcare Materials, 15, e2502567. https://doi.org/10.1002/adhm.202502567.
[19] Guo, Q., Li, S., Zhou, X., Liu, T., Zhang, Z., Liu, L., Jiang, X., Wang, Y., Liang, X., & Wang, Y. (2021). Sequential release of pooled siRNAs and paclitaxel by aptamer-functionalized shell-core nanoparticles to overcome paclitaxel resistance of prostate cancer. ACS Applied Materials & Interfaces, 13(12), 13990–14003. https://doi.org/10.1021/acsami.1c01687.
[20] Wang, C., Guan, S., Liu, J., Liu, J., Chen, J., Zhang, W., Wang, J., Zhang, H., Zhang, L., & Zhang, Q. (2022). Lipid-coated albumin-paclitaxel nanoparticles loaded with sorcin-siRNA reverse cancer chemoresistance via restoring intracellular calcium ion homeostasis. Journal of Nanobiotechnology, 20, 319. https://doi.org/10.1186/s12951-022-01521-4.
[21] Chen, Z. W., Kang, F. P., Xie, C. K., Liao, C. Y., Li, G., Wu, Y. D., Lin, H. Y., Zhu, S. C., Hu, J. F., Lin, C. F., Huang, Y., Tian, Y. F., Huang, L., Wang, Z. W., & Chen, S. (2023). A novel Trojan horse nanotherapy strategy targeting the cPKM-STMN1/TGFB1 axis for effective treatment of intrahepatic cholangiocarcinoma. Advanced Science, 10(47), e2303814. https://doi.org/10.1002/advs.202303814.
[22] Yang, D., Zhan, J., Miao, L., He, C., & Xu, H. (2025). Lipid nanoparticle-mediated mRNA/siRNA dual-bioengineered dendritic cell vaccines combined of PD-1/PD-L1 blockade for boosting tumor immunotherapy. Materials Today Bio, 35, 102357. https://doi.org/10.1016/j.mtbio.2025.102357.
[23] Zhang, Y., et al. (2025). Multi-functional lipid nanoformulations for enhancing the efficacy of mRNA tumor vaccines by reversing tumor immunosuppressive microenvironment. Nano Today, 63, 102757. https://doi.org/10. 1016/ j. nantod.2025.102757.
[24] Zhou, J., Li, Y., Jiang, X., Xin, Z., Liu, W., Zhang, X., Zhai, Y., Zhang, Z., Shi, T., Xue, M., Zhang, M., & Wu, Y. (2025). PD-L1 siRNA incorporation into a cationic liposomal tumor mRNA vaccine enhances cytotoxic T cell activation and prevents immune evasion. Materials Today Bio, 31, 101603. https://doi.org/10.1016/j.mtbio.2025.101603.
[25] Uzel, A., Bélanger, P., Sirois, J., Pourcelet, É., Marois, A., & Fortin, M. A. (2023). Single pulse nanosecond laser-stimulated targeted delivery of anti-cancer drugs from hybrid lipid nanoparticles containing 5 nm gold nanoparticles. Small, 19(48), e2305591. https://doi.org/10.1002/smll.202305591.
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