Effect of NP properties

NP PropertyOutcome/Effect (Example)
SizeReduced opsonization and RES uptake at <200 nm
Affects transport (transvascular and interstitial) and retention (enhanced in tumors for 50–200 nm NP)
Internalization of inorganic NP and liposomes (maximum at 30–50 nm)
Intracellular trafficking/processing
Surface chargeAffects opsonization (rapid RES clearance of cationic liposomes)
Affects electrostatic interaction with vessel pore
Promotes interactions with ECM components, reduces interstitial transport
Increases binding to cell membrane and internalization (positively charged NP shows higher binding and internalization compared with neutral or negatively charged NP)
Biomaterial and surface modificationCoating with hyaluronic acid reduces immunogenicity
Cationic cell-penetrating peptide promotes NP internalization and perinuclear localization
Collagenase and hyaluronidase alter ECM, promote interstitial transport
Ligands for targeting (e.g., folate, transferrin, CD19, CD20, uPAR, HER2) enhances uptake and accumulation
pH-sensitive fusogenic polymers, peptides, or lipids enhance cargo release in endosomes
Shape and geometryHigher curvature leads to a larger degree of membrane wrapping
Higher uptake of spherical NP vs. rod-shaped NP in murine macrophages and human HeLa cells
Higher uptake of nanorods with shorter aspect ratio (length-to-width) in HeLa and human breast MCF7 cells vs. longer ratio, whereas the opposite was found for cationic crosslinked pegylated hydrogel NP in HeLa cells
Lower uptake for smaller NP (100 and 300 nm) vs. larger NP with the same aspect ratio
For mesoporous silica NP, spherical NP uses clathrin-mediated endocytosis, whereas the rod- or worm-shaped analogs prefer macropinocytosis
Gold nanorods align to cell membrane in a near-parallel manner followed by rotating by ∼90° to enter the cell via a caveolae-mediated pathway
Molecular dynamic simulations suggest slow membrane wrapping of NP with sharp edges or high curvature (e.g., cubes)
Shape of NP affects biodistribution; for example, 1) longer circulation for higher aspect ratio NP (e.g., filomicelles, rods) vs. spherical NP; 2) discoidal/plate-like NP accumulate in the heart and lungs, presumably due to the margination under flow leading to the accumulation on vascular walls; and 3) spheres and short rods tend to accumulate more in the liver than longer rods, whereas NP with a higher aspect ratio concentrate more in the spleen and lungs
  • Readers are referred to earlier reviews (Wang et al., 2010; Li et al., 2012; Andar et al., 2014; Shang et al., 2014; Paliwal et al., 2015; Treuel et al., 2015; Au et al., 2016; Yang et al., 2016; Behzadi et al., 2017; Kinnear et al., 2017) for more details and the original citations. HER, human epidermal growth factor receptor; uPAR, urokinase-type plasminogen activator receptor.