TABLE III.
Examples investigating the biological activity of nanoparticles in the presence of biofluids. ApoA4/C3/H, apolipoprotein A4/C3/H; BPEI, branched polyethylenimine; pDNA, plasmid DNA; FBS, fetal bovine serum; FCS, fetal calf serum; hb-PG, hyper-branched polyglycerol; HP, human plasma; HS, human serum; i.v., intravenous; LNPs, lipid nanoparticles; LPEI, linear polyethylenimine; ND, not determined; NPs, nanoparticles; mAB, monoclonal antibody; PC, protein corona; PEG, polyethylene glycol; PEI, polyethylenimine; siRNA, small interfering RNA; SPIONs, superparamagnetic iron oxide NPs; Tf, transferrin; hTf, human Tf. Cell lines: 1321N1, human brain astrocytoma cell line; ECV 30, spontaneously transformed, human umbilical vein endothelial cell line; H441, human lung adenocarcinoma cell line; HEK293, human embryonic kidney cells; HeLa, human cervix carcinoma cells; hMSCs, human mesenchymal stem cells; Huh7, human hepatocellular carcinoma cell line; J774, murine macrophage cell line; MCF-7, human breast adenocarcinoma; N2a, murine neuroblastoma cell line Neuro2a; PC3, human prostate carcinoma cell line; RAW264.7, murine monocyte/macrophage-like cell line.
| Nanoparticles | Biofluid | Protein corona | Biological impact | Reference |
|---|---|---|---|---|
| Cellular uptake and internalization | ||||
| Polystyrene NPs | 10% FBS, static vs dynamic incubation | Dynamic incubation: protein-enriched corona (esp. plasminogen) | Dynamic incubation: reduced binding to HeLa cells | 26 |
| Unmodified LNPs | 50% FBS, static vs dynamic incubation | Dynamic incubation: increased levels of α1-antitrypsin in the PC | Dynamic incubation: increased uptake in HeLa cells, whereas decreased uptake in MCF-7 cells | 27 |
| Differently functionalized polystyrene NPs | HS, ratio of total particle-surface area to serum concentration = 5 ml/m2 | ApoH-enriched PC | Increased uptake in HeLa cells and hMSCs | 193 |
| ApoA4- and ApoC3-enriched PC | Decreased uptake in HeLa cells and hMSCs | |||
| Liposomes modified with PEG or hb-PG | 5% and 100% HP | neglectable PC formation | PEG: decreased uptake in RAW264.7 cells; hb-PG: increased uptake in RAW264.7 cells | 29 |
| Targeting capability | ||||
| hTf-functionalized silica NPs | 10% FBS | ND | Abolished targeting efficiency | 34 |
| Tf-modified virus-like nanoparticles | 55% FBS, murine, or chicken serum | Minor PC formation | No effect on targeting efficiency | 256 |
| 55% HS | Reduced targeting efficiency (competing hTf) | |||
| mAB-conjugated liposomes | CD-1 mouse plasma in vitro vs in vivo | Amount of adsorbed proteins comparable for in vitro and in vivo PC, but in vivo PC composition more complex | No full inhibition of the targeting efficiency for the in vivo PC, but for the in vitro PC | 93 |
| Drug release | ||||
| 4-nitroanisole loaded polymeric nanocapsules | 10% or 100% FBS | ND | Minimal change in release profile | 53 |
| Tamoxifen-loaded SPIONs | 10% or 100% FBS | ND | Reduced burst effect | |
| Albumin-bound paclitaxel drug (Abraxane®) | 10% or 100% FBS or HP | ND | ||
| Transfection efficiency | ||||
| Carboxymethyl poly(L-histidine)/poly(β-amino ester) (PbAE)/pDNA ternary complexes | 5 – 50% FBS | ND | HEK293 cells: improved serum resistance and gene transfer | 257 |
| PEG-coated polyplex micelles loaded with bundled mRNA | 50% FBS | ND | Improved serum stability and transfection efficiency (Huh7 cells) | 250 |
| T-shape oligoaminoamides/pDNA complexes | 45%, 90% FBS | ND | N2a and Huh7 cells: decreased transfection efficiency in high serum due to inhibited lytic activity | 12 |
| Gene transfectants histone H1 and cationic lipid DOSPER | > 10% FCS | ND | ECV 304 cells: inhibited transfection efficiency, remedy by addition of calcium ions or chloroquine | 258 |
| Tyrosine-modified LPEI 10 kDa/siRNA complexes | 50% FCS | ND | H441 cells: no decrease in transfection efficiency | 251 |
| Tyrosine-modified disulfide-crosslinked BPEI 2 kDa/pDNA complexes | 50% FCS | ND | PC3 cells: no decrease in transfection efficiency | 252 |
| Toxicity | ||||
| Cationic polystyrene NPs | 10% fluorescent labeled FBS | ND | 1321N1 cells: reduced cytotoxicity due to masked cationic charges | 259 |
| Silica and polystyrene NPs | 90% HP | Rapidly formed PC containing >300 different proteins | Reduced hemolysis, thrombocyte activation, and endothelial cell death | 56 |
| Magnetic NPs | 2.5%, 10%, 40% HS | ND | No hemolytic effect | 260 |
| Silver NPs | 1 or 10% FBS | Strongly attached PC | J774 cells: decreased cytotoxicity due to sulfidation | 55 |
| PEI 5 kDa; PEI 25 kDa PEG-free and PEGylated (2 kDa, 20 kDa; different grafting degrees (1; 10)) | In vitro: HS; in vivo: pig model, i.v. injection | In vitro: formation of the complement terminal complex (SC5b-9); in vivo: cardiopulmonary changes in pigs | In vitro: complement activation only for PEG-free PEI 25 kDa; in vivo: PEG of ≥ 20 kDa may be favorable in terms of less complement activation | 25 |