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已发表论文
mRNA 脂质纳米颗粒在癌症疫苗中的关键临床前沿问题
Authors Cao L, Min J, Yu M, Zhang Z, Yuan D, Chen D
Received 5 September 2025
Accepted for publication 19 November 2025
Published 12 December 2025 Volume 2025:20 Pages 14935—14953
DOI https://doi.org/10.2147/IJN.S565558
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Farooq A. Shiekh
Lili Cao,1 Jie Min,2 Meipin Yu,1 Zhongfeng Zhang,1 Dan Yuan,1 Dingchao Chen3
1Department of Plastic Surgery, The Affiliatied Hospital of Jiaxing University (Zhejiang Rongjun Hospital), Jiaxing, Zhejiang, People’s Republic of China; 2General Surgery Department, Jiaxing No.1 Hospital, Jiaxing, Zhejiang, People’s Republic of China; 3General Surgery Department, The Affiliatied Hospital of Jiaxing University (Zhejiang Rongjun Hospital), Jiaxing, Zhejiang, People’s Republic of China
Correspondence: Dingchao Chen, Email chendc0830@163.com
Abstract: Cancer vaccines are promising, but clinical translation is constrained by inefficient antigen delivery and suboptimal immune activation. Lipid nanoparticles (LNPs)-validated for potency and safety in COVID-19 mRNA vaccines-offer a versatile, scalable, and immunogenic platform. Key barriers persist: precise targeting of tumors or lymphoid tissues, efficient intracellular mRNA release, and the immunosuppressive tumor microenvironment. This review synthesizes design principles for mRNA-loaded LNPs, emphasizing lipid chemistry, organ-selective biodistribution, and nano-engineering strategies that strengthen antigen presentation and T-cell priming. We also examine combination approaches with checkpoint blockade, chemotherapy-induced immunogenic cell death, and molecular adjuvants. Clinically, signals of efficacy are emerging-most notably the KEYNOTE-942 study, in which mRNA-4157 combined with pembrolizumab showed a sustained improvement in recurrence-free survival at 5 years compared with pembrolizumab alone-highlighting both the potential and the remaining questions for this modality. Finally, we outline manufacturing and regulatory considerations and map future directions-including thermostable formulations, self-amplifying RNA, and AI-guided lipid discovery-to address translational bottlenecks and expand global access to LNP-based cancer vaccines.
Keywords: lipid nanoparticles, mRNA cancer vaccines, organ-selective delivery, immunotherapy, nanomedicine
1Department of Plastic Surgery, The Affiliatied Hospital of Jiaxing University (Zhejiang Rongjun Hospital), Jiaxing, Zhejiang, People’s Republic of China; 2General Surgery Department, Jiaxing No.1 Hospital, Jiaxing, Zhejiang, People’s Republic of China; 3General Surgery Department, The Affiliatied Hospital of Jiaxing University (Zhejiang Rongjun Hospital), Jiaxing, Zhejiang, People’s Republic of China
Correspondence: Dingchao Chen, Email chendc0830@163.com
Abstract: Cancer vaccines are promising, but clinical translation is constrained by inefficient antigen delivery and suboptimal immune activation. Lipid nanoparticles (LNPs)-validated for potency and safety in COVID-19 mRNA vaccines-offer a versatile, scalable, and immunogenic platform. Key barriers persist: precise targeting of tumors or lymphoid tissues, efficient intracellular mRNA release, and the immunosuppressive tumor microenvironment. This review synthesizes design principles for mRNA-loaded LNPs, emphasizing lipid chemistry, organ-selective biodistribution, and nano-engineering strategies that strengthen antigen presentation and T-cell priming. We also examine combination approaches with checkpoint blockade, chemotherapy-induced immunogenic cell death, and molecular adjuvants. Clinically, signals of efficacy are emerging-most notably the KEYNOTE-942 study, in which mRNA-4157 combined with pembrolizumab showed a sustained improvement in recurrence-free survival at 5 years compared with pembrolizumab alone-highlighting both the potential and the remaining questions for this modality. Finally, we outline manufacturing and regulatory considerations and map future directions-including thermostable formulations, self-amplifying RNA, and AI-guided lipid discovery-to address translational bottlenecks and expand global access to LNP-based cancer vaccines.
Keywords: lipid nanoparticles, mRNA cancer vaccines, organ-selective delivery, immunotherapy, nanomedicine