Journal of controlled release : official journal of the Controlled Release SocietyFeb 4, 2026

Large and low-PEG lipid nanoparticles improve delivery to immune cells for strong mRNA cancer vaccines

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

Large low-PEG lipid nanoparticles improved dendritic-cell targeting for a preclinical mRNA cancer vaccine platform.

Evidence

This mRNA vaccine platform experiment engineered enlarged low-PEG LNPs and tested GFP and HPV16 E6E7 mRNA delivery, reporting about 82% of GFP-positive cells as dendritic cells, about 44% of CD11c dendritic cells expressing GFP, and tumor regression at 1 microgram doses.

Caveat

The abstract reports immune and antitumor endpoints for a preclinical HPV16 E6E7 model, not human clinical efficacy or safety.

Simplified

Efficient delivery of messenger RNA (mRNA) to dendritic cells (DCs) remains a major challenge limiting the efficacy of mRNA cancer vaccines. Here, we report a large-sized lipid nanoparticle (LLNP) platform specifically engineered for enhanced DC targeting. By reducing PEG-lipid content to 0.3% and proportionally increasing the concentrations of structural lipids and mRNA sixfold relative to the Moderna classic formulation, we generated LLNPs with enlarged size and optimized surface properties that favor DC uptake. Following intravenous administration, LLNPs achieved markedly enhanced mRNA expression in DCs, with ~82% of GFPcells identified as DCs and ~ 44% of CD11cDCs expressing GFP. LLNPs also promoted DC maturation and antigen presentation. LLNP-mediated delivery of HPV16 E6E7 mRNA elicited robust effector and memory cytotoxic T lymphocyte responses, enabling effective tumor regression at doses as low as 1 μg. Both conventional type 1 dendritic cells (cDC1) and conventional type 2 dendritic cells contributed to antigen presentation, with cDC1 playing the predominant role. Compared with BioNTech's RNA-lipoplex delivery platform, LLNPs demonstrated superior DC transfection, T cell activation, and antitumor efficacy. Collectively, these findings establish LLNPs as a robust and versatile platform for next-generation mRNA cancer vaccines with enhanced therapeutic potential. + +