Table 2.
Effects of nanoparticles on clotting in vitro. Sizes of nanoparticles have been determined in different conditions (as produced and in the media in which they were applied). Data were obtained from exposure with human blood samples. Platelet activation obtained by dynamic and not in static exposure is marked by asterisk (*).
| Material | Size (nm) | Effect on Platelets | Effects Plasmatic Coagulation | Reference | |
|---|---|---|---|---|---|
| Carbon, metal and metal oxide nanoparticles | |||||
| Silver (Ag) | |||||
| 10-15 | inhibition of platelet aggregation | [69] | |||
| 16 | no effect on platelet aggregation (+/- agonist) | thrombin generation decreased, aPTT prolonged | [70] | ||
| 20 | inhibition of platelet aggregation | [71] | |||
| 24 | inhibition of intrinsic pathway | [72] | |||
| 30 | platelet activation, * | XIIa-like activity, activation of clotting | [73] | ||
| 10-100 | platelet activation and aggregation, * | [47] | |||
| 90-240 | platelet activation | induction of clot formation | [74] | ||
| Boron phosphate (BPO4), plain not folate | 180-280 | Platelet aggregation by plain, * | [75] | ||
| Gold (Au) | |||||
| solid | 9 | platelet activation | [76] | ||
| solid | 5-30 | inhibition of platelet aggregation (+/- agonist) | [77] | ||
| solid | 18>68 | platelet activation, * | [78] | ||
| solid | 18 | no effect on activation and aggregation, * | [38] | ||
| solid, cationic and anionic | 30 | no effect on platelet aggregation | [79] | ||
| solid | 50 | no effect on platelet aggregation (+/- agonist) | [80] | ||
| solid | 30, 50 | binding to fibrinogen; no effect on coagulation | [81] | ||
| solid | >60 | inhibition of platelet aggregation (+/- agonist) | [77] | ||
| solid | <60 | platelet aggregation (+ agonist) | [78] | ||
| shells | 2-3 | inhibition of platelet aggregation | [82] | ||
| shells | 15 | platelet aggregation | [82] | ||
| shells | 150 | platelet aggregation | [82] | ||
| hollow spheres | 63 | no effect on platelet aggregation (+/- agonist) | [83] | ||
| Nanodiamonds, carboxylated | 4-10 | platelet aggregation | [48] | ||
| 5;100 | no effect on PT and aPTT | [84] | |||
| CdTe, thioglycylic acid-, cystamine-capped | 2.6-4.8 | Platelet activation and aggregation, * | [85] | ||
| CdSe, cysteine-capped | 15 | platelet aggregation | [86] | ||
| C60 | |||||
| composite | 10 | no effect on platelet activation (+ agonist), * | [87] | ||
| Polyhydroxylated C60 | 7 | platelet aggregation (+ agonist) | [88] | ||
| Single-walled carbon nanotubes (SWCNTs) | |||||
| plain | not given | platelet aggregation | [51] | ||
| carboxylated> carboxylated+PEG | < 2 | platelet aggregation | accelerated clot formation | [89] | |
| Carboxylated> carboxylated+PEG | < 2 | platelet aggregation | [90] | ||
| Multi-walled carbon nanotubes (MWCNTs) | |||||
| Plain | 60-100 x 1000-2000 | platelet aggregation, release of microparticles, * | [91] | ||
| carboxylated | not given | platelet aggregation | [51] | ||
| Carboxylated, long>short | 10 x 223, 10 x 926 | platelet activation | accelerated fibrin formation, decreased clot formation, and reduced clot hardness | [92] | |
| amidated, long>short | 10 x 223, 10 x 926 | platelet activation | accelerated fibrin formation, decreased clot formation, and reduced clot hardness | [92] | |
| Plain>carboxylated | 15 x 1000-2000 | platelet aggregation | [93] | ||
| carboxylated | 26-31 x 490-580 | platelet activation | intrinsic pathway activation | [52] | |
| Amidated | 26-31 x 490-580 | platelet activation | extrinsic pathway activation | [52] | |
| Iron (Fe) | |||||
| Iron carbide, carboxylated, IgG, ProtA coated | 30 | no effect on platelet activation, * | activation of clotting: IgG and ProtA>carboxylated | [94] | |
| iron carbide, carbon coated | 33 | activation of clotting | [95] | ||
| Ferucarbotran (Resovist) | 30-90 | slight effect on activation, no effect on aggregation, * | [96] | ||
| Fe2O3; Fe3O4 | 55-65; 20-30 | no effect on platelet activation | no effect on clot formation | [74] | |
| Fe2O3 coated with poly-vinyl pyridine | 80 | intrinsic pathway inhibition | [97] | ||
| Fe3O4@nSiO2, heparin coated | 100 | no effect on PT and aPTT | [98] | ||
| Polystyrene (PS) | |||||
| carboxylated | 26 | no effect on intrinsic pathway | [99] | ||
| Carboxylated | 24, 220 | intrinsic pathway activation | [100] | ||
| aminated | 24, 220 | decreased thrombin generation by FXII, IX depletion | [100] | ||
| Neutral | 20, 200 | no effect on platelet aggregation | [93] | ||
| carboxylated, amidated | 20, 200 | platelet activation and aggregation, * | [101] | ||
| Aminated, not carboxylated | 60 | platelet activation and aggregation | [50] | ||
| neutral | 60 | no effect on activation and aggregation, * | [38] | ||
| Amidated | 60-80 | platelet aggregation | [102] | ||
| carboxylated | 60-80 | platelet activation and aggregation | [102] | ||
| Carboxylated, aminated, neutral | 50, 100 | platelet aggregation | [103] | ||
| carboxylated | 220 | intrinsic pathway activation | [99] | ||
| Anionic > cationic latex | 300 | platelet aggregation | [104] | ||
| neutral, latex | 200-400 | platelet aggregation | [105] | ||
| Silica (SiO2) | |||||
| amorphous | 15 | no effect on PT and aPTT, clotting induced | [106] | ||
| Amorphous | 10, 50, 150, 500 | platelet activation, 10>50 nm | [37] | ||
| amorphous | 30 | no effect on activation, * | no effect on clotting time | [94] | |
| Amorphous | 50 | platelet adhesion and aggregation, * | [107] | ||
| amorphous | 10, 50 | platelet activation, 10 not 50 nm, * | [38] | ||
| Amorphous, cationic and anionic | 70, 232 | induction of clotting | [108] | ||
| bare and PEGylated ORMOSIL | 35, 45 | factor XII activation, activation intrinsic pathway | [109] | ||
| Mesoporous, pluronic polymer capped | 107, 149 | no effect on PT and aPTT | [110] | ||
| Titanium dioxide (TiO2) | |||||
| Rutile | 10 x 40 | no effect on activation and aggregation | [50] | ||
| rutile | 20-160 | no effect on activation | no effect on clot formation | [74] | |
| zinc oxide (ZnO), cationic and anionic | 70, 232 | induction of clotting | [108] | ||
| Biodegradable Nanoparticles | |||||
| cetyl alcohol/polysorbate, +/- PEG, anionic | 119, 133 | inhibition of platelet aggregation | [111] | ||
| Dendrimers | |||||
| Amine G1-G4 PAMAM dendrimers | 2.2-4.5 | prolonged clotting time and decreased initial clotting velocity | [112] | ||
| carboxylated, hydroxylated, amine G3-G6 PAMAM dendrimers | 3.1-7.5 | platelet activation and aggregation, large amine, * | [113] | ||
| Amine G7 PAMAM dendrimers | 8.1 | platelet activation | platelet-dependent thrombin generation inhibited | [114] | |
| Liposomes | |||||
| Cationic | not given | inhibition of platelet aggregation (+ agonist), no effect without | [115] | ||
| anionic, neutral | not given | no effect on platelet aggregation (-/+ agonist) | [115] | ||
| Cationic | 180-200 | platelet activation | [116] | ||
| Poly(lactic-co-glycolic acid), PLGA | |||||
| PLGA-macrogol and chitosan | 100-500 | no effect on platelet aggregation (+/- agonist) | [117] | ||
| Anionic PLGA and PLGA-chitosan | 580-640 | no effect on activation and aggregation, weak inhibition of aggregation (+ agonist) | [118] | ||
| PLGA-alendronate | 200 | no effect on platelet aggregation and activation | [119] | ||
| poly(ɛ-caprolactone) lipid-core nanocapsules, chitosan coated | 476 | no effect on platelet aggregation | no effect on PT and aPTT | [120] | |
| Chitosan | |||||
| cationic | 430-580 | no effect on activation and aggregation, weak inhibition of aggregation (+ agonist), * | [118] | ||
| Chitosan, plain, PEG | 140; 105 | platelet activation of bare not of PEG-coated particles | no effect on PT and aPTT | [121] | |