Table 3.

Overview of highlights in NP-mediated targeted delivery of biotherapeutics recently used to attenuate atherosclerosis.

Biotherapeutic Delivered (Target)	NP Targeting Moiety	NP Material	Result	Reference
siRNA (ICAM-1)	in vivo phage display-identified peptide targeting NMHC IIA	B-PEI crosslinked with added disulfide bonds and conjugated to peptide via heterobifunctional PEG	NPs target athero-prone regions and lead to ICAM-1 knock-down	[59]
siRNA (ICAM-2)	None, but preferentially accumulates in pulmonary ECs	Hydrophobically modified (C13) PEI formed into liposome-like NPs with PEG incorporated	Significant in vitro and in vivo mRNA silencing in endothelial cells for a variety of vascular pathologies, particularly Lewis Lung Carcinoma (LLC).	[67]
Ac2-26 peptide from Annexin A1 (N-formyl peptide receptor FPR2/ALX)	Collagen IV-binding peptide	PLGA bioconjugated to PEG and peptide	NPs target athero-prone regions and reduce lesion size, oxidative stress, increase collagen, and enhance athero-protective effects.	[38]
Interleukin-10 (IL-10 receptor)	Collagen IV-binding peptide	PLGA-PLA copolymer with PEG coating and bioconjugated peptide	NPs target athero-prone regions and reduce lesion size, cap thickness, neutrophil infiltration, and immune cell responses to inflammatory stimuli.	[39]
Anti-miRNA (miR-712, known association with MMPs)	VCAM-1 targeting peptide	Liposomes formed from cationic lipids, PEG-lipids, and peptide-PEG-lipids	Specific targeting of ECs in vivo under oscillatory/low shear stress leading to decreased plaque size, increased cap size, and decreased destructive enzymatic activity.	[51]
MiRNA (miR-146a and miR-181b)	E-selectin targeting peptide	PEG-g-PEI:miRNA NPs encapsulated within silicon microparticles	Improved relaxation of vascular endothelium ex vivo, reduced chemotactic ligand expression/monocyte adhesion in addition to lesion/collagen area and macrophage, while increasing SMC migration.	[60]