Table 1.

Features of primary phagocytic receptors responsible for nanoparticle-mediated cellular uptake.

Receptor Type	Receptor Subtype	Receptor Description
Toll-like Receptors	TLR 1,2,4,5,6	Located on surface of phagocytes [105]
	TLR 3,7,8, 9	Found within intracellular compartments [105]
	TLR 2,3,7	Induce cell survival or inflammatory reducing mechanisms such as autophagy [106, 107]
	TLR 4	Detects LPS, a common contaminant arising from bacterial adsorption on nanoparticles and is recognized by TLR4 surface receptors and activates inflammasome production [108, 109]. Initiates inflammation to remove pathogens [110, 111].
Mannose/Lectin Receptors		Recognize complex carbohydrates, detecting mannose, glucose or sugar structures on pathogenic material and glycoproteins [112].
	C-type lectin	Have been engaged by decorating NP surfaces with di-mannose and galactose [113]
	Sugar lectin-mannose	Interactions with macrophages can be harnessed with nanoparticulates decorated with large numbers of sugar-like motifs [114, 115]
	Mannan	Has been used to coat gelatin nanoparticles to increase specificity of delivery of didanosine to macrophages for the treatment of HIV [116]. These nanoparticles substantially increased the amount of drug delivered to the brain, lymphatics and splenic tissue regions, increasing specificity of delivery and decreasing systemic side effects [117].
	Mannose (CD206)	Targets Th2 polarized macrophages for certain chronic inflammatory disease states [118, 119].
	Carbohydrate surface modification	Utilized to help direct tumor targeting of mesoporous silica nanomaterials for thermoablative therapy, which reduced tumor size significantly compared to control in treated animals [120].
Scavenger receptors		Implicated in non-specific macrophage-nanoparticle uptake [18, 121] Could increase phagocytic recognition and decreased circulation potential. Responsible for the recognition and internalization of foreign pathogens, oxidized or acetylated native proteins (i.e., low density lipoproteins (LDLs) and maleylated albumin) and apoptotic cellular debris [122]. Recognition and uptake of NP in macrophages has been linked to inflammation-induced nanoparticle toxicity [18]. Play a primary role in the recognition and identification of LPS on gram-negative bacteria and lipoteichoic acid on the surface of gram-positive bacteria (both common contaminants on the surface of nanoparticles) [123]. Extensive testing should be performed on NP to ensure surfaces are free of LPS
	SR-AI/II scavenger receptors	Can be targeted using poly anionic ligands [124]. Uptake superparamagnetic iron oxide nanoparticles coated with non-aggregated dextran, a poly anionic sugar (Dextran-SPIO) [87]. However, when the particles were coated with a proprietary polymer brush, uptake via these receptors was significantly diminished or eliminated [43, 87, 125]. Could be silenced to reduce silica NP uptake [18].
	MARCO	Macrophage receptor with collagenous structure has been linked to the uptake of polystyrene nanoparticles [121] within alveolar macrophages as well as aggregates of iron oxide [126].
Fc Receptors (CD64 )		Recognize the Fc region of IgG, one of the most abundant proteins in the human body and a vital part of the innate and humoral immune systems [127]. IgG adsorption to the surface of nanoparticles is well characterized [128–130], Induce phagocytosis[127]