Table 1.
IONs with cationic and anionic coatings that are internalized through adsorptive interactions with the PM.
| Coating | Structure | Zeta Potential (mV) | Hydrodynamic Diameter Water (nm) 1 | Hydrodynamic Diameter Serum (nm) 1 | Cell Viability (24 h) | Main Endocytic Mechanism(s) | Internalized Tissue | Ref |
|---|---|---|---|---|---|---|---|---|
| Cationic | ||||||||
| Chitosan (CS) | Core-shell | ~4.2 | ~122.4 | Not reported | ≥90% at 30 µg/mL NPs a | Clathrin-dependent | Rat NSCs | [97] |
| CS-thioglycolic acid | Core-shell | 21 ± 5.27 | 94 ± 20 | 91 ± 8 nm | ≥80% at 300 µg/mL NPs a | Not specified | Human umbilical cord EPCs | [127] |
| Poly(vinylalcohol/vinylamine) | Core-shell | Positive | ~24 | Not reported | ~100% (up to 123 µg/mL Fe) a | Clathrin-dependent | Me300 | [128] |
| [129] | ||||||||
| diethylaminoethyl-dextran (DEAE-DEX) | Core-shell | ~26 | ~150 | Not reported | ≥90% (up to 500 µg/mL Fe) a | Clathrin- and caveolin-independent Macropinocytosis | A-549 | [130] |
| PEI-Zonyl FSA/DNA | Core-shell | ~52.2 (w/o DNA) |
144 ± 0.2 | Not reported | ≥80% (up to 0.1 µM Fe)b | Caveolin-dependent Clathrin-dependent | HEK293 | [131] |
| PEI-Pluronic F-127/DNA | Core-shell | ~61.7 (w/o DNA) |
160 ± 1.4 | Not reported | ≥80% (up to 0.05 µM Fe) b | Caveolin-dependent Clathrin-dependent | HEK293 | [132] |
| Lactosylated N-alkyl-PEI2k | Micellar | ~28.7 | 75 ± 6 | Not reported | ~100% (up to 15 µg/mL Fe) b | Not specified | RAW 264.7 | [122] |
| PEI-stearic acid/PEG-poly(L-glutamic acid) | Polymeric nanosphere | ~8 | 150 ± 25 | Not reported | ~100% (up to 6.3 µg/mL Fe) b | Not specified | MSCs | [126] |
| PEI/siRNA | Core-shell | ~25.7 (w/o siRNA) |
~43.56 | Not reported | ≥90% at 2 µg/mL NPs (w/o siRNA) a | Not specified | U-87 & U-251 | [98] |
| ≤50% at 2 µg/mL (anti-tumor siRNA) a | ||||||||
| PEI-decorated poly(glycidyl methacrylate) | Polymeric nanosphere | Positive | ~160 | Not reported | ~100% (up to 250 µg/mL NPs) b | Clathrin- and caveolin-independent | Rat PC12 | [132] |
| PEG-g-PEI/siRNA | Core-shell | 34.38 ± 1.66 | 93.8 ± 0.6 | Not reported | Non-significant cytotoxicity | Not specified | SGC-7901 | [124] |
| 15.1 ± 0.64 (siRNA) | ||||||||
| PEI-dextran/miRNA | Core-shell | 32.5 ± 0.62 (w/o miRNA) | 148.67 ± 1.52 | Not reported | ≥80% (up to 150 µg/mL NPs) a | Not specified | U2 | [133] |
| PEG-g-Chitosan/PEI/siRNA | Core-shell | 19.6 ± 5.7 (siRNA) | 111.9 ± 52.4 | ~115 nm | Non-significant cytotoxicity (concentration not specified) | Not specified | Rat C6 | [134] |
| Lipofectamine-Endoderm | Core-shell | −2.45 ± 0.53 * | ~181 (PBS) | Not reported | ≥80% (up to 50 µg/mL Fe) a,b | Clathrin-dependent Macropinocytosis | HeLa | [135] |
| Poly-L-lysine (PLL) | Core-shell | ~16.9 | ~24 | Not reported | ≥90% (up to 25 µg/mL NPs) a | Not specified | NSCs | [136] |
| PLL-dextran | Core-shell | 50 ± 2 | 115 ± 30 | Not reported | ≥80% (at 24 µg/mL NPs) a | Not specified | HepG2 | [137] |
| Maltodextrin | 25 ± 1.5 | 60 ± 13.1 | Not reported | Not reported | Clathrin-dependent | 16HBE14o | [138] | |
| D6DOM/pDNA | Core-shell | 9 ± 1.2 | 71 ± 12 | 146 ± 29 nm | ≥90% a and ≥85% b (up to 47 µg/mL NPs) | Not specified | MKN-74 & NUGC-4 | [139] |
| gH625-cysteine-PEG-Cy5.5 | Core-shell | ~4.08 | 97.8 ±1.2 | Not reported | Non-significant cytotoxicity | Not specified | MDA-MB-231 | [140] |
| PF14-SCO/Chitosan | Core-shell | ~37 | ~370 | Not reported | Non-significant cytotoxicity | Not specified | HeLa | [141] |
| PF1221-SCO/Chitosan | Core-shell | ~23 | ~420 | Not reported | Non-significant cytotoxicity | Not specified | HeLa | [141] |
| Poly(maleic anhydride-alt-1-decene)-dimethylamino propylamine- Protamine/siRNA | Core-shell | 30.5 ± 2 | ~30 | Not reported | ≥90% (up to 65 nM NPs) a | Not specified | MCF-7, U251 | [142] |
| 26.4 ± 3 (siRNA) | ||||||||
| Anionic | ||||||||
| PEG-b-poly(e-caprolactone)-g-poly(acrylic acid) | Core-shell | −29 ± 1.9 | 208.5 ± 4.6 | Not reported | ~100% (up to 500 µg/mL NPs) a | Clathrin-dependent | CRL-5802 | [143] |
| DNA-PEG | Core-shell | −25.2 ± 0.8 | 55.8 ± 7.7 | 74.7 ± 4.4 | ≥80% (up to 100 µg/mL NPs) a | Clathrin- and caveolin-independent Phagocytosis Clathrin-dependent Macropinocytosis SR-A involved |
RAW 264.7 | [144] |
| Carboxy-dextran | Core-shell | ~−8.02 | ~60.32 | Not reported | ≥90% (up to 100 µg/mL Fe) a | Clathrin-dependent Macropinocytosis SR-A involved |
Human macrophages | [145] |
| Carboxymethyl- dextran | Core-shell | ~−48 | 45 ± 7 | Not reported | Not reported | Macropinocytosis Caveolin-dependent Clathrin-dependent | Caco2 | [146] |
| Dextran sulfate | Core-shell | ~−45 | ~60 | Not reported | ≥90% (up to 5 mM NPs) | Not specified SR-A involved |
BV2 | [147] |
| Silica | Core-shell | ~−59 | ~17 | ~136 | Non-significant cytotoxicity (50 µg/mL Fe) | Caveolin-dependent | HeLa | [148] |
| PEG-silane | Core-shell | ~−14 | ~30 | ~157 | Non-significant cytotoxicity (50 µg/mL Fe) | Caveolin-dependent Clathrin- and caveolin-independent Macropinocytosis | HeLa | [148] |
| Carboxilic acid-silane | Core-shell | ~47 | ~30 | ~133 | Non-significant cytotoxicity (50 µg/mL Fe) | Caveolin-dependent | HeLa | [148] |
| Dimercapto-succinate (DMSA) | Core-shell | −49 ± 2 −9 ± 1 (serum) |
65 ± 4 | 128 ± 54 | Not reported | Clathrin-dependent Macropinocytosis | Rat microglial cells | [149] |
| Dimercapto-succinate (DMSA) | Core-shell | −44 ± 14 −14 ± 5 (serum) |
50 ± 2 | 116 ± 13 | ≥90% up to 2 mM NPs (6 hrs) b | Clathrin-dependent | Cerebellar granule neurons | [150] |
| Dimercapto-succinate (DMSA) | Core-shell | Not reported | ~10 | Not reported | ~100% (up to 50 µg/mL NPs) a | Clathrin-dependent Caveolin-dependent Macropinocytosis SR-A involved |
RAW 264.7 | [151] |
| Glucose | Core-shell | ~−40 | 40–45 (PBS) | Not reported | ≥90% (up to 100 µg/mL NPs) b | Caveolae-dependent | Vero cells | [152] |
| N-(trimethoxysilyl propyl) ethylenediamine triacetate | Core-shell | −39 ± 3 | ~8 | Not reported | Not reported | Caveolae-dependent | Mouse BMECs | [153] |
| None | - | ~−35 | 20–200 | Not reported | ≥90% (up to 50 µg/mL NPs) a | Clathrin-dependent | Caco2 | [154] |
| MamC-DOXO | Core-shell | 9.6 ± 1 | 36 ± 12 | 11–300 nm | ≥90% up to 30 µg/mL NPs (w/o DOXO) a | Not specified | HUVECs, KBV1, HeLa | [155] |
| −7 ± 0.3 (serum) | ≤50% for more than 10 µg/mL NPs (DOXO) a | |||||||
| Rhodium citrate | Core-shell | −35 ± 6 | 120 ± 1 | Not reported | Not reported | Clathrin-dependent | MDA-MD231, MCF7 | [156] |
| Citrate | Core-shell | Negative (not specified) | 8.7–11 | Not reported | Not reported | Clathrin-dependent Caveolin-dependent | HUVECs | [157] |
1 Hydrodynamic diameter measured with DLS. * Authors explain slight negative surface potential due to uneven binding of lipofectamine and only local positive charges. a Viability was reported according to metabolic activity of cells and b membrane permeabilization. D6DOM: DC-6-14 (O,O’-ditetradecanoyl-N-(α-trimethlammonioacetyl) diethanolamine chloride) and 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) (1:0.4); SCO: Splice correction oligonucleotide; Caco-2: human epithelial colorectal adenocarcinoma; HUVEC: Human umbilical vein endothelial cells; KBV1: multi-drug resistant human cervical cancer; HeLa: Human cervical adenocarcinoma; MDA-MB-231: Breast carcinoma; MCF7: Breast carcinoma; BMECs: Brain microvessel endothelial cells; CRL-5802: Human non-small cell lung cancer; RAW 264.7: Macrophages; BV2: Microglia; U251: Human glioblastoma astrocytoma; MKN-74: Gastric adenocarcinoma; NUGC-4: Gastric adenocarcinoma; MSCs: Mesenchymal stem cells; U87: Glioblastoma cells; PC12: pheochromocytoma neural progenitor; HEK293: Human embryonic kidney; A549: Human lung adenocarcinoma; Me300: Human melanoma cells; U2: osteosarcoma; HepG2: Liver hepatocellular carcinoma; NSCs: neural stem cells; SGC-7901: gastric carcinoma; C6: glioblastoma; EPCs: endothelial progenitor cells.