The lipid nanomicelles incorporating peptide vaccine and SN38 prodrug potentiate neoadjuvant chemo-immunotherapy.
4 affiliations
- 1School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
- 2Hunan Provincial Key Laboratory of Animal Models and Molecular Medicine, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, School of Biomedical Sciences, Hunan University, Changsha, Hunan, 410082, China.
- 3Yunnan Digestive Endoscopy Clinical Medical Center, Department of Gastroenterology, The First People's Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, China.
- 4State Key Laboratory of Respiratory Diseases, Guangzhou, 511436, China.
Abstract
Neoadjuvant regimens often fail to eliminate micrometastases due to profound immunosuppression and the limited immunogenicity of residual tumor cells. In this work, a versatile lipid nanoplatform was engineered to orchestrate potent chemotherapy with in situ neoantigen vaccination. Unlike conventional physical encapsulation, an arginine-modified SN38 prodrug (SN38-Arg) was synthesized to enhance amphiphilicity and facilitate the co-assembly with PEGylated lipids and tumor-specific peptides (HPV16 E7 or Adpgk). This design yields uniform ~115 nm nanomicelles with exceptional stability and > 60% peptide encapsulation efficiency. Mechanistically, these nanomicelles leverage folate-receptor targeting to achieve dual synchronization: SN38-Arg induces Topoisomerase I inhibition and extensive DNA damage, while simultaneously promoting dendritic cell maturation and antigen cross-presentation. In neoadjuvant murine models of HPV+ TC-1 and MSI-high MC38 tumors, a brief preoperative course of SFE/SFA not only significantly debulked primary tumors but, critically, prevented postsurgical recurrence of treated cohorts and established long-term protective memory T cell reservoirs. This was accompanied by a remodeled tumor immune microenvironment marked by elevated CD8⁺ T cell infiltration and the reduction of regulatory T cells and MDSCs, all without discernible systemic toxicity. This work establishes a clinically translatable, off-the-shelf nanomicellar strategy that integrates SN38-based chemotherapy with peptide vaccination, offering a compelling avenue to improve pathological complete response rates and long-term disease-free survival in surgical oncology.
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BibTeX
@article{guo2026lipid,
title = {{The lipid nanomicelles incorporating peptide vaccine and SN38 prodrug potentiate neoadjuvant chemo-immunotherapy.}},
author = {Jiaxin Guo and Miaoyan Liu and Ping Wan and Yang Zhou and Dexu Luo and Xueheng Wu and Zhiyi Zhou and Xiaowei Huang and Chengzhi Jin and Xin Deng and Jialong Qi and Wenjie Chen},
journal = {International journal of pharmaceutics: X},
year = {2026},
month = oct,
doi = {10.1016/j.ijpx.2026.100681},
url = {https://europepmc.org/article/MED/42921442},
note = {CC BY},
}
RIS
TY - JOUR
TI - The lipid nanomicelles incorporating peptide vaccine and SN38 prodrug potentiate neoadjuvant chemo-immunotherapy.
AU - Jiaxin Guo
AU - Miaoyan Liu
AU - Ping Wan
AU - Yang Zhou
AU - Dexu Luo
AU - Xueheng Wu
AU - Zhiyi Zhou
AU - Xiaowei Huang
AU - Chengzhi Jin
AU - Xin Deng
AU - Jialong Qi
AU - Wenjie Chen
PY - 2026
DA - 2026/10/09
JO - International journal of pharmaceutics: X
DO - 10.1016/j.ijpx.2026.100681
UR - https://europepmc.org/article/MED/42921442
AB - Neoadjuvant regimens often fail to eliminate micrometastases due to profound immunosuppression and the limited immunogenicity of residual tumor cells. In this work, a versatile lipid nanoplatform was engineered to orchestrate potent chemotherapy with in situ neoantigen vaccination. Unlike conventional physical encapsulation, an arginine-modified SN38 prodrug (SN38-Arg) was synthesized to enhance amphiphilicity and facilitate the co-assembly with PEGylated lipids and tumor-specific peptides (HPV16 E7 or Adpgk). This design yields uniform ~115 nm nanomicelles with exceptional stability and > 60% peptide encapsulation efficiency. Mechanistically, these nanomicelles leverage folate-receptor targeting to achieve dual synchronization: SN38-Arg induces Topoisomerase I inhibition and extensive DNA damage, while simultaneously promoting dendritic cell maturation and antigen cross-presentation. In neoadjuvant murine models of HPV+ TC-1 and MSI-high MC38 tumors, a brief preoperative course of SFE/SFA not only significantly debulked primary tumors but, critically, prevented postsurgical recurrence of treated cohorts and established long-term protective memory T cell reservoirs. This was accompanied by a remodeled tumor immune microenvironment marked by elevated CD8⁺ T cell infiltration and the reduction of regulatory T cells and MDSCs, all without discernible systemic toxicity. This work establishes a clinically translatable, off-the-shelf nanomicellar strategy that integrates SN38-based chemotherapy with peptide vaccination, offering a compelling avenue to improve pathological complete response rates and long-term disease-free survival in surgical oncology.
SN - 2590-1567
ER -