European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical SciencesAug 18, 2026

Lipid-based trastuzumab modification improves delivery of mRNA nanoparticles to HER2-positive cancer cells

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Aug 19, 2026

Abstract

Trastuzumab-modified mRNA/lipid nanoparticles (LNPs) demonstrated over 100-fold greater cellular association in HER2-overexpressing SKOV-3 cells compared to unmodified LNPs.

LNPs are a promising delivery system for mRNA therapeutics but often lack cell-type specificity.
Orientation-controlled modifications with antibodies may enhance the targeted delivery of nucleic acids.
Trastuzumab, an anti-HER2 antibody, was used to modify mRNA/LNPs for selective delivery to HER2-overexpressing cancer cells.
In a mouse model with SKOV-3 tumors, trastuzumab-modified mRNA/LNPs led to significantly higher luciferase expression compared to unmodified and isotype-controlled groups.
These results indicate the potential of trastuzumab modification for improving mRNA delivery in HER2-positive cancers.

Simplified

Lipid nanoparticles (LNPs) have emerged as a key delivery platform for mRNA therapeutics, as demonstrated by the clinical success of mRNA vaccines against SARS-CoV-2. LNPs are now being investigated for various applications, such as cancer immunotherapy and the treatment of genetic disorders. However, LNPs tend to accumulate predominantly in the liver and lack intrinsic cell-type specificity. Modifying LNPs with antibodies is a promising strategy for enhancing cell-specific delivery. We have previously developed orientation-controlled anti-transferrin receptor and anti-PD-L1 antibody modifications for the targeted delivery of nucleic acids, including mRNA and siRNA. In this study, we newly applied this platform to trastuzumab, a clinically established high-affinity anti-HER2 therapeutic antibody, to develop orientation-controlled trastuzumab-modified mRNA/LNPs for HER2-selective delivery. we evaluated trastuzumab-modified mRNA/LNPs in HER2-overexpressing SKOV-3 ovarian cancer cells and HER2-low MDA-MB-231 breast cancer cells. Trastuzumab-modified mRNA/LNPs exhibited over 100-fold greater cellular association than unmodified LNPs in cultured HER2-overexpressing SKOV-3 cells. Furthermore, after intratumoral administration in a mouse model bearing subcutaneous SKOV-3 tumors, the trastuzumab-modified group showed significantly higher luciferase expression than the unmodified and isotype-controlled antibody-modified groups. These findings support FcBP-HFQ lipid-mediated trastuzumab modification of LNPs as a useful approach for efficient cell-selective mRNA delivery.

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Lipid-based trastuzumab modification improves delivery of mRNA nanoparticles to HER2-positive cancer cells

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