NP Property | Outcome/Effect (Example) |
---|---|
Size | Reduced 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 charge | Affects 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 modification | Coating 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 geometry | Higher 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.