Modular antibody-functionalized poly(β-amino ester) polyplexes: Colloidal and interfacial design for targeted mRNA...

Area of Science:

• Biotechnology
• Nanomedicine
• Polymer Chemistry

Background:

• Effective polymer-nucleic acid nanoparticle design needs control over stability, interface, and assembly.
• Targeted delivery of messenger RNA (mRNA) requires robust nanocarriers.

Purpose of the Study:

• To create a modular, antibody-functionalized polyplex nanoplatform for targeted mRNA delivery.
• To enhance nanoparticle stability and introduce modular targeting capabilities.

Main Methods:

• Hierarchical assembly of poly(β-amino ester) (PβAE-447) and mRNA into polyplexes.
• Coating polyplexes with a poly(γ-glutamic acid)-avidin (PGA-avidin) corona for stability and functionalization.
• Conjugating biotinylated antibodies via avidin-biotin interactions for modular targeting.

Main Results:

• Nanoparticles exhibited controlled size, charge reversal, and endosomal pH buffering.
• Antibody-functionalized nanoparticles showed receptor-dependent uptake and mRNA expression in human T cells.
• A balance between transfection efficiency and cytocompatibility was observed.

Conclusions:

• A modular design framework for polymer-mRNA nanoparticles with tunable interfaces was established.
• The nanoplatform supports targeted and non-viral gene delivery applications.
• This approach offers precise control for advanced nanomedicine development.