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

被引：0
作者：
Younis, Mahmoud A. [1 ,2 ,3 ]
Sato, Yusuke [2 ,4 ]
Elewa, Yaser H. A. [5 ,6 ]
Harashima, Hideyoshi [1 ,2 ]
机构：
[1] Hokkaido Univ, Fac Pharmaceut Sci, Lab Innovat Nanomed, Kita 12,Nishi 6,Kita Ku, Sapporo 0600812, Japan
[2] Hokkaido Univ, Inst Vaccine Res & Dev IVReD, Kita 21,Nishi 11,Kita ku, Sapporo 0010021, Japan
[3] Assiut Univ, Fac Pharm, Dept Ind Pharm, Assiut 71526, Egypt
[4] Hokkaido Univ, Fac Pharmaceut Sci, Lab Mol Design Pharmaceut, Kita 12,Nishi 6,Kita ku, Sapporo 0600812, Japan
[5] Zagazig Univ, Fac Vet Med, Dept Histol & Cytol, Zagazig 44511, Egypt
[6] Hokkaido Univ, Fac Vet Med, Kita 18,Nishi 9,Kita ku, Sapporo 0600818, Japan
来源：
DRUG DELIVERY AND TRANSLATIONAL RESEARCH | 2025年
关键词：
Anticancer vaccine; Antigen-presenting cells; Lipid nanoparticles; mRNA; Clinical translation; SIRNA; NEUTROPHILS; PHENOTYPE;
D O I：
10.1007/s13346-025-01824-w
中图分类号：
TH7 [仪器、仪表];
学科分类号：
0804 ; 080401 ; 081102 ;
摘要：
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 similar to 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.
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页数：16
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