Colloids and surfaces. B, BiointerfacesMay 29, 2026

Custom antibody-coated particles designed to deliver mRNA specifically to human T cells

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated May 30, 2026

Abstract

Antibody-functionalized nanoparticles were developed for targeted messenger RNA delivery with controlled size and charge properties.

A biodegradable cationic polymer efficiently condenses messenger RNA into nanoscale structures.
Coating with a poly(γ-glutamic acid)-avidin layer enhances stability and allows for modular targeting.
Biotinylated antibodies can be attached without affecting the core of the nanoparticles.
Nanoparticles exhibit size control and buffering behavior in conditions mimicking endosomal pH.
Targeted nanoparticles showed receptor-dependent uptake and expression in human T cells.
Delivery efficiency is influenced by varying biological conditions, balancing transfection efficiency and cytocompatibility.

Simplified

The rational design of polymer-nucleic acid nanoparticles requires precise control over colloidal stability, interfacial structure, and assembly under biologically relevant conditions. Here, we report a hierarchically assembled, antibody-functionalized polyplex nanoplatform for targeted messenger RNA (mRNA) delivery. A biodegradable cationic poly(β-amino ester) (PβAE-447) enables efficient condensation of in vitro-transcribed mRNA into nanoscale polyplexes. To enhance stability and introduce modular functionality, polyplexes were coated with a poly(γ-glutamic acid)-avidin (PGA-avidin) corona, forming a core-shell structure that suppresses aggregation and provides a chemically addressable interface. Biotinylated antibodies were conjugated via avidin-biotin interactions, enabling modular targeting without altering the nanoparticle core. The resulting nanoparticles exhibit controlled size, charge reversal, and buffering behavior in the endosomal pH range. Using CCR4-IRES-ZsGreen mRNA, antibody-functionalized nanoparticles demonstrated receptor-dependent uptake and expression in human T cells. Although delivery efficiency varied with biological conditions, the system reveals a balance between transfection efficiency and cytocompatibility. The reported study establishes a modular design framework for polymer-mRNA nanoparticles with tunable interfaces, supporting targeted and non-viral gene delivery applications.

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Competing interests

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The author is NOT an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for this journal and was not involved in the editorial review or the decision to publish this article. No financial interests.

PubMed

Custom antibody-coated particles designed to deliver mRNA specifically to human T cells

Abstract

Full Text

Funding

Competing interests

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