Table 1.

Targeting cell populations in different locations

Targeting strategy	Targeted cells	Route of administration	Platform	Size and shape	Modifications	Notes	Refs.
Tissue-specific	DCs	Subcutaneous	PLGA	~1 µm and ~30 µm spheres	Loading of TGFβ1, GM-CSF, vitamin D3, type II collagen and insulin	Larger particles recruit and condition DCs through release of GM-CSF and TGFβ1. Simultaneously, smaller loaded particles are phagocytosed by local DCs at the injection site for reprogramming and migrate to lymph node	85,86
				~800 nm spheres	TGFβ surface modifications and loading of OVA323–339 peptide	Co-stimulatory particles are phagocytosed by local DCs for immune reprogramming	88
		In vitro study	Polystyrene	150 nm and 2 µm spheres, 3× stretched rods from 150 nm and 2 µm spheres	Physical absorption of poly I:C or CL264	Spherical particles show stronger DC activation than rod-shaped particles. Nanospheres promote the strongest activation	200
	Lymph-node-resident immune cells (such as DCs or T cells)	Intranodal	PLGA	~5 µm and ~ 300 nm spheres	Loading of poly I:C	PLGA particles reach the lymph node through direct injection. Microparticles release poly I:C at the site of injection for sustained DCs activation. By contrast, nanoparticles are rapidly phagocytosed by lymph-node-resident DCs and macrophages	201
				~3–4 µm spheres	Loading of MOG peptide and rapamycin	Intranodal injection of microparticles to promote polarization of T cells	89
	Local phagocytic immune cells (such as macrophages)	In vitro study	PU	~35 nm and ~63 nm spheres	Negative and positive surface charge	Inhibition of M1 macrophage polarization after uptake of negatively charged nanoparticles	92
			Ac-DEX	~829 nm spheres	Loading of rapamycin	Particles are phagocytosed by activated macrophages, reducing production of pro-inflammatory molecules through pH-dependent release of rapamycin from particle matrix	93
			Polystyrene	0.5–3 µm spheres; major axis 0.35–2.5 μm, minor axis 0.2–2 μm rods; major axis 0.35–2.5 μm, minor axis 0.2–2 μm disks	–	Disk-shaped and spherical particles show enhanced macrophage uptake compared to elongated particles	152
Vasculature	Activated endothelial cells	Intravenous	Polystyrene	500 nm and 2 μm spheres; 500 nm ESD (AR = 6) and 2 μm ESD (AR = 4) rods	sLea and anti-VCAM1 surface modification	Targeted rod-shaped microparticles adhere at a higher rate than targeted microspheres to inflamed aortic segments and plaque	154
			PLGA	~200 nm spheres	γ3 peptide surface modification and loading of sparfloxacin and tacrolimus	Targeted nanoparticles concentrate antibacterial and anti-inflammatory drugs at site of inflammation (lungs)	95
			PAE	100 nm spheres	Anti-ICAM1 surface modification and loading of TPCA-1	Targeted nanoparticles concentrate in the inflamed lungs and release anti-inflammatory drug from pH-responsive polymer matrix	97
		In vitro study	Polystyrene, silica and titania	500 nm spheres	sLea surface modification	Dense nanoparticles adhere to inflamed HUVEC at a higher rate than neutrally buoyant nanoparticles	113
Circulating white blood cells	Circulating phagocytes	Intravenous	Polystyrene, PLG, HPPS	2 µm, 500 nm and 15 nm spheres	Unloaded or drug-loaded particles	Particles passively target phagocytes in the bloodstream to divert them from sites of inflammation	109,115,116
		Intraperitoneal or intravenous	PLGA and PLA	~400 nm spheres	Varied surfactants and molecular weight of polymer for fabrication	Physiochemical properties of the particles influenced immunomodulatory effects	114
		In vitro study	Polystyrene	0.5–2 µm spheres	Carboxylated, PEGylated or sLea-coated particles	Collisions in blood flow, particle binding to endothelium, and particle phagocytosis were found to reduce leukocyte adhesion to inflamed endothelium in blood flow	175
	Neutrophils	Intravenous	PolyA	1 µm spheres	Polymerized salicylic acid	PolyA particle treatment in ALI and ARDS reduces inflammatory damage in lungs and enhance survival compared to PLGA and polystyrene particles	117
		In vitro study	PLGA	1–3 µm spheres or 1.5 µm (long axis) rods	–	Physical properties of particles preferentially target neutrophils through larger size or rod shape	119,120

Ac-DEX, acetalated dextran; ALI, acute lung injury; AR, aspect ratio; ARDS, acute respiratory distress syndrome; CL264, adenine analogue; DC, dendritic cell; ESD, equivalent spherical diameter; GM-CSF, granulocyte–macrophage colony-stimulating factor; HPPS, high-density lipoprotein-mimicking peptide-phospholipid scaffold; HUVEC, human umbilical vein endothelial cell; ICAM1, intracellular cell adhesion molecule 1; MOG, myelin oligodendrocyte glycoprotein; OVA, ovalbumin; PAE, poly(β-amino ester); PLG, poly(lactide-co-glycolide); PLGA, poly(lactic-co-glycolic acid); PolyA, PolyAspirin; poly I:C, poly(inosinic:cytidylic acid); PU, polyurethane; sLe^a, sialyl Lewis A; TGFβ1, transforming growth factor β1; TPCA-1, 2-[(aminocarbonyl)-amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide; VCAM1, vascular cell adhesion molecule 1.