Table 2.

PBAE nanoparticle functionalization strategies

Design Strategy of Ligand Incorporation	Added Functionality	Ligand
Polyglutamic (PGA)-coated nanoparticles for electrostatic incorporation	Cell-targeted DNA delivery to primary endothelial cells	RGD peptide [84]
	T cell-targeted DNA delivery	Anti-CD3e f(ab´)2 [35]
	Cell-targeted mRNA delivery to T cells and hematopoietic stem cells (HSCs)	Anti-CD3, anti-CD8, and anti-CD105 [85]
	Macrophage-targeted mRNA delivery	Mannose [86]
Covalently incorporated in PBAE structure	Targeted DNA delivery to APCs	Mannose [82,100,103]
	Targeted mRNA delivery to APCs	Oligopeptide [83]
	Improved mucus penetration and DNA transfection in the lungs	PEG (5 kDa) [114]
	Improved in vivo transfection of nucleic acid-based adjuvant after IP administration	PEG (2 kDa) [77]
	Shielding to enhance tissue diffusivity	PEG [78]
Ligand functionalized lipid incorporated via hydrophobic interactions	Improved cellular internalization and DNA transfection, reduced toxicity, and increased DNA loading	Cell-penetrating peptides (CPPs) mTAT, bPrPp, and MPG [115]
	Minimized toxicity for safe and effective mRNA transfection of dendritic cells (DCs)	PEGylated lipid [65]
	Shielding to improve colloidal stability and prevent aggregation in serum for potent mRNA transfection after systemic administration	PEGylated lipid [25,80,81,97,116]
	Steric stabilization	Pluronic F-108 [92]