International journal of pharmaceuticsApr 29, 2026

Peptide-Enhanced Lipid Nanoparticles Delivering IL-12 mRNA and PD-L1 siRNA for Brain Tumor Immunotherapy

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

RGD-modified LNPs may improve brain delivery of combined IL-12 mRNA and PD-L1 siRNA immunotherapy for glioblastoma.

Evidence

Preclinical delivery experiments compared in vivo biodistribution of RGD, AP2, RVG29, FA, and Tf LNPs and assessed RLNP immunotherapeutic efficacy against GBM.

Caveat

The abstract does not specify the glioblastoma model, sample size, durability, or safety outcomes, limiting translation of the BBB-targeting signal.

Simplified

Lipid nanoparticles (LNPs) have emerged as the most advanced nucleic acid delivery vehicles in clinical applications, achieving successful targeting of major organs such as the liver, spleen, and lungs. However, efficient penetration of the blood-brain barrier (BBB) continues to be a key obstacle for brain-targeted applications. In this study, we developed a peptide modified LNPs system for the co-delivery of IL-12 mRNA and PD-L1 siRNA to achieve combined immunotherapy against glioblastoma (GBM). This dual-nucleic-acid delivery strategy simultaneously activates pro-inflammatory immune responses and suppresses immune checkpoint pathways, thereby alleviated the highly suppressed GBM microenvironment. By comparing the in vivo biodistribution of LNPs modified with various peptides (RGD, AP2, RVG29, FA, and Tf), we found that RGD modified LNPs (RLNPs) exhibited the strongest luciferase signal in the brain, indicating superior BBB penetration. Overall, RLNPs demonstrated enhanced brain-targeting capability and improved immunotherapeutic efficacy, suggesting that this delivery strategy provides a promising platform for central nervous system therapeutics.