2. Academic Validation
  3. Harnessing the composition of lipid nanoparticles to selectively deliver mRNA to splenic immune cells for anticancer vaccination

Harnessing the composition of lipid nanoparticles to selectively deliver mRNA to splenic immune cells for anticancer vaccination

  • Drug Deliv Transl Res. 2025 Oct;15(10):3626-3641. doi: 10.1007/s13346-025-01824-w.
Mahmoud A Younis 1 2 3,  Yusuke Sato 4 5,  Yaser H A Elewa 6 7,  Hideyoshi Harashima 8 9
Affiliations

Affiliations

  • 1 Laboratory of Innovative Nanomedicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo, 060-0812, Japan. mahmoudyounis@aun.edu.eg.
  • 2 Institute of Vaccine Research and Development (IVReD), Hokkaido University, Kita 21, Nishi 11, Kita-ku, Sapporo, 001-0021, Japan. mahmoudyounis@aun.edu.eg.
  • 3 Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt. mahmoudyounis@aun.edu.eg.
  • 4 Institute of Vaccine Research and Development (IVReD), Hokkaido University, Kita 21, Nishi 11, Kita-ku, Sapporo, 001-0021, Japan.
  • 5 Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo, 060-0812, Japan.
  • 6 Department of Histology and Cytology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44511, Egypt.
  • 7 Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan.
  • 8 Laboratory of Innovative Nanomedicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo, 060-0812, Japan. harasima@pharm.hokudai.ac.jp.
  • 9 Institute of Vaccine Research and Development (IVReD), Hokkaido University, Kita 21, Nishi 11, Kita-ku, Sapporo, 001-0021, Japan. harasima@pharm.hokudai.ac.jp.
PMID: 40055249 DOI: 10.1007/s13346-025-01824-w
Abstract

Herein, we report a design for lipid nanoparticles (LNPs) that specifically delivers mRNA to splenic immune cells post intravenous administration for potential Anticancer vaccination applications. A diverse library of ionizable lipids was screened in vivo, in combination with various helper lipids, where the composition of LNPs was tweaked to control their in vivo performance. The biodistribution of the LNPs was then investigated at both organ and sub-organ levels. Subsequently, the LNPs were recruited to deliver an Anticancer mRNA-based vaccine to mice. The in vivo tropism of the LNPs was dramatically affected by the chemical structure of the ionizable lipids in question, where a model lipid, CL15H6, was recognized as displaying high affinity for the spleen. Further optimization of the composition of the LNPs enabled highly efficient and spleen-selective mRNA delivery, where the optimized CL15H6 LNPs demonstrated a high capacity for homing to splenic antigen-presenting cells (APCs). Furthermore, loading the LNPs with a low dose of ovalbumin-encoding mRNA (mOVA), as a model antigen, protected the mice against OVA-expressing tumor challenges and suppressed the tumor growth in tumor-bearing mice by ~ 75%, which was superior to the results of a clinically-relevant formulation. The CL15H6 LNPs proved to be biosafe upon either acute dose escalation or repeated administrations. The novel and scalable platform reported herein is promising for clinical translation as a neoantigen vaccine.

Keywords

Anticancer vaccine; Antigen-presenting cells; Clinical translation; Lipid nanoparticles; mRNA.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-173245
    生化试剂
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z