Table 2.
Environmental and experimental settings influencing the formation, composition, and characteristics of the PC.
| Feature | Influence on NP interactions with proteins | References | |
|---|---|---|---|
| Medium | Protein amount | • Total proteins amount in the medium affect the thickness and composition of PC. | Zhang et al., 2017 Partikel et al., 2019 |
| Composition | • Biofluids' origin (e.g., interstitial fluid, blood, plasma, serum) influences the PC composition. • The presence of cell culture medium can influence PC composition. |
Bonvin et al., 2017 Cox et al., 2018 Ho et al., 2018 Berardi and Baldelli, 2019 |
|
| Source | • The species of animal (e.g., rat, bovine, or human) affect the PC composition. • In samples from humans, inter-individual variability (age, sex, diet, and health state) have shown to influence PCs. |
Corbo et al., 2017b; Solorio-Rodríguez et al., 2017 |
|
| Temperature and pH | • Temperature of incubation influences the protein diffusivity and the affinity toward NPs. • pH can influence NPs and protein surface charge and reciprocal affinity |
Raoufi et al., 2018 Gorshkov et al., 2019 |
|
| Time | • Following the Vroman effect, the time of incubation is a critical parameter, especially for short time points, since the protein-binding dynamics change very quickly within a few minutes of incubation. | Tenzer et al., 2013 Hadjidemetriou et al., 2016 |
|
| Fluidics | • Dynamic conditions (especially PC formed after in vivo administration) give a much more realistic representation of the actual PC composition and are more heterogeneous. • PC conformation is less homogeneous upon dynamic conditions, leaving portion of the NPs not coated and free to interact with cells. |
Hadjidemetriou et al., 2015 Hadjidemetriou et al., 2019 Pozzi et al., 2016 |
|
| Isolation technique | • Centrifugation may remove loosely bound proteins from the NPs, thus providing only a rough picture of the hard PC. • Strong centrifugation could destabilize less dense NPs, such as liposomes, by mechanical stress. • A combination of size exclusion chromatography and filtration represents a good alternative to centrifugation. |
Carrillo-Carrion et al., 2017 | |