A nanoparticle platform for the co-delivery of multiple antigen epitope peptides and STING agonist to lymph nodes for cancer immunotherapy

Xiyu Ke; Brady A Campbell; Xiaoya Lu; Betul Celiker; Lei Zheng; May Tun Saung; Hai-Quan Mao

doi:10.1016/j.ijpharm.2025.125757

A nanoparticle platform for the co-delivery of multiple antigen epitope peptides and STING agonist to lymph nodes for cancer immunotherapy

Int J Pharm. 2025 Jul 25:680:125757. doi: 10.1016/j.ijpharm.2025.125757. Epub 2025 May 25.

Authors

Xiyu Ke¹, Brady A Campbell², Xiaoya Lu¹, Betul Celiker³, Lei Zheng⁴, May Tun Saung⁵, Hai-Quan Mao⁶

Affiliations

¹ Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA.
² The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Pancreatic Cancer Precision Medicine Center of Excellence, Johns Hopkins University School of Medicine, Baltimore, MD, USA; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: lzheng6@jhmi.edu.
⁵ The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Pancreatic Cancer Precision Medicine Center of Excellence, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: msaung1@jhmi.edu.
⁶ Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address: hmao@jhu.edu.

PMID: 40425059
PMCID: PMC12167128 (available on 2026-07-25)
DOI: 10.1016/j.ijpharm.2025.125757

Abstract

Nanoparticles loaded with cancer epitope peptides have shown great potential for cancer immunotherapy. However, preparing small-sized nanoparticles with a narrow size distribution for the co-delivery of multiple antigen peptides has been a challenge. The lack of scalable and reproducible nanoparticle preparation methods has also hindered the widespread application of nanoparticles in cancer immunotherapy. In this study, we developed lymph node-targeted nanoparticles for the co-delivery of a group of sixteen pancreatic cancer antigen peptides and a STING agonist as an adjuvant using the flash nanocomplexation (FNC) method. The nanoparticles generated by FNC had a smaller particle size and a narrower size distribution compared to the nanoparticles prepared by bulk mixing. The FNC-generated nanoparticles enhanced human monocyte activation, demonstrated lymph node-targeting effect, and activated dendritic cells in vivo, all without any observable toxicity. Additionally, in vivo studies demonstrated the strong anti-tumor efficacy of these nanoparticles in an orthotopic pancreatic cancer mouse model. This nanoparticle platform enables the effective co-delivery of multiple antigen epitope peptides and an adjuvant to the lymph nodes. Furthermore, the scalability and reproducibility of the FNC method could facilitate the rapid clinical translation of this nanoparticle platform.

Keywords: Cancer immunotherapy; Cancer vaccine; Nanoparticle formulation; Pancreatic cancer; STING agonist.

MeSH terms

Adjuvants, Immunologic / administration & dosage
Animals
Antigens, Neoplasm* / administration & dosage
Antigens, Neoplasm* / immunology
Cell Line, Tumor
Dendritic Cells / drug effects
Dendritic Cells / immunology
Epitopes* / administration & dosage
Epitopes* / immunology
Female
Humans
Immunotherapy / methods
Lymph Nodes* / drug effects
Lymph Nodes* / immunology
Lymph Nodes* / metabolism
Membrane Proteins* / agonists
Mice
Mice, Inbred C57BL
Nanoparticles* / administration & dosage
Nanoparticles* / chemistry
Pancreatic Neoplasms* / immunology
Pancreatic Neoplasms* / therapy
Particle Size
Peptides* / administration & dosage

Substances

Membrane Proteins
Antigens, Neoplasm
STING1 protein, human
Peptides
Epitopes
Adjuvants, Immunologic

Abstract

MeSH terms

Substances

Grants and funding