Abstract
Here, we present a thorough study of pegylated silica nanoparticle (SNP) interaction with different biological environments. The SNPs have a mean diameter of about 40 nm and are coated with polyethylene glycol (PEG) of different molecular weights. The physicochemical characterization of SNPs allowed the confirmation of the binding of PEG chains to the silica surface, the reproducibility of the synthesis and the narrow size-dispersion. In view of clarifying the SNP interaction with biological environments, we first assessed the SNP reactivity after the incubation with two cell lines (macrophages RAW 264.7 and primary human fibroblasts), observing a reduced toxicity of pegylated SNPs compared to the bare ones. Then, we investigated the effect of the protein adsorption on the SNP surface using the model serum protein, bovine serum albumin (BSA). We found that the protein adsorption takes place more heavily on poorly pegylated SNPs, promoting the uptake of the latter by macrophages and leading to an increased mortality of these cells. To better understand this mechanism by means of flow cytometry, the dye Ru(bpy)3Cl2 was incorporated in the SNPs. The overall results highlight the SNP potentialities as a drug delivery system, thanks to the low interactions with the macrophages.
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References
Alexander GB, Heston WM, Iler RK (1954) The solubility of amorphous silica in water. J Phys Chem 58:453–455
ASTM International (1988) Standard Test Method for Silica in Water. ASTM International, West Conshohocken
Braun K, Pochert A, Beck M, Fiedler R, Gruber J, Lindén M (2016) Dissolution kinetics of mesoporous silica nanoparticles in different simulated body fluids. J Sol-Gel Sci Technol 79:319–327
Del Pino P, Pelaz B, Zhang Q, Maffre P, Nienhausand GU, Parak WJ (2014) Protein corona formation around nanoparticles-from the past to the future. Mater Horiz 1:301–313
Fröhlich E (2012) The role of surface charge in cellular uptake and cytotoxicity of of medical nanoparticles. Int J Nanomedicine 7:5577–5591
Guo Z, Meng S, Zhong W, Du Q, Chou LL (2009) Self-assembly of silanated poly(ethylene glycol) on silicon and glass surfaces for improved haemocompatibility. Appl Surf Sci 255(15):6771–6780
Graf C, Gao Q, Schütz I, Noufele CN, Ruan W, Posselt U, Korotianskiy E, Nordmeyer D, Rancan F, Hadam S, Vogt A, Lademannv J, Haucke V, Rühl E (2012) Surface functionalization of silica nanoparticles supports colloidal stability in physiological media and facilitates internalization in cells. Langmuir 28(20):7598–7613
Harper GR, Davies MC, Davis SS, Tadros TF, Taylor DC, Irving MP, Waters JA (1991) Steric stabilization of microspheres with grafted polyethylene oxide reduces phagocytosis by rat Kupffer cells in vitro. Biomaterials 12(7):695–700
Jo S, Park K (2000) Surface modification using silanated poly(ethylene glycol)s. Biomaterials 21:605–616
Kopelman R, Xu H, Yan F, Monson EE, Tang W, Schneider R, Philbert M (2002) Preparation and characterization of poly(ethylene glycol)-coated Stöber silica nanoparticles for biomedical applications. SPIE (International Society of Photonic Engineering) Proc 4626:383–393
Lee JA, Kim MK, Paek HJ, Kim YR, Kim MK, Lee JK, Jeong J, Choi SJ (2014) Tissue distribution and excretion kinetics of orally administrated silica nanoparticles in rats. Int J Nanomedicine 9:251–260
Lenher V, Merrill HB (1917) The solubility of silica. J Am Chem Soc 39(12):2630–2638
Liu D, Lin B, Shao W, Zhu Z, Ji T, Yang C (2014) In vitro and in vivo studies on the transport of PEGylated silica nanoparticles across the blood-brain barrier. ACS Appl Mater Inter 6(3):2131–2136
Laysan Bio Inc. Material safety data sheet. (2013)
Okner R, Domb AJ, Mandler D (2009) Electrochemically deposited poly(ethylene glycol)-based sol-gel thin films on stainless steel stent. New J Chem 33:1596–1604
Owens DE 3rd, Peppas NA (2006) Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm 307(1):93–102
Phillips E, Penate-Medina O, Zanzonico PB, Carvajal RD, Mohan P, Ye Y, Humm J, Gonen M, Kalaigian H, Schoder H, Strauss HW, Larson SM, Wiesner U and Bradbury S, (2014) Clinical translation of an ultrasmall inorganic optical-PET imaging nanoparticle probe. Sci Transl Med 6(260):260ra149
Poteser M, Wakabayashi I (2004) Serum albumin induces iNOS expression and NO production in RAW 264.7 macrophages. Brit J Pharmaco 143(1):143–151
Rahman M, Laurent S, Tawil N, Yahia L, Mahmoudi M (2013) Protein-nanoparticle interactions: the bio-nano interface. Springer Series in Biophysics 15:21–44
Rimer JD, Trofymluk O, Navrotsky A, Vlachos DG (2007) Kinetic and thermodynamic studies of silica nanoparticle dissolution. Cem Mater 19(17):4189–4197
Romberg B, Henninkand WE, Storm G (2008) Sheddable coatings for long circulating nanoparticles. Pharm Res 25(1):55–71
Sadzuka Y, Nakade A, Hirama R, Miyagishima A, Nozawa Y, Hirota S, Sonobe T (2008) Effects of mixed polyethyleneglycol modification on fixed aqueous layer thickness and antitumor activity of doxorubicin containing liposome. Int J Pharm 238(1–2):1711–1180
Sahneh FD, Scoglio C, Riviere J (2013) Dynamics of nanoparticle-protein corona complex formation: analytical results from population balance equations. PLoS One 8(5):e64690
Selvestrel F, Moret F, Segat D, Woodhams JH, Fracasso G, Rio Echevarria IM, Baù L, Rastrelli F, Compagnin C, Reddi E, Fedeli C, Papini E, Tavano R, Mackenzie A, Bovis M, Yaghini E, MacRobert AJ, Zanini S, Boscaini A, Colombatti M, Mancin F (2013) Targeted delivery of photosensitizers: efficacy and selectivity issues revealed by multifunctional ORMOSIL nanovectors in cellular systems. Nanoscale 5(13):6106-6116
Stöber W, Fink A and Bohn E, (1968) Controlled growth of monodisperse silica sphere in the micron size range. Journal of Colloid and Interface Science26:62–69
Tang L, Cheng J (2013) Nonporous silica nanoparticles for nanomedicine application. Nano Today 8(3):290–312
Tenzer S, Docter D, Kuharev J, Musyanovych A, Fetz V, Hecht R, Schlenk F, Fischer D, Kiouptsi K, Reinhardt C, Landfester K, Schild H, Maskos M, Knauer SK, Stauber RH (2013) Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology. Nat Nanotechnol 8(10):772–781
Veronese FM, Pasut G (2005) PEGylation, successful approach to drug delivery. Drug Discov Today 10(21):1451–1458
Xie G, Sun J, Zhong G (2012) Tissular localization and excretion of intravenously administered silica nanoparticles of different sizes. J Nanopart Res 14:671–679
Xu H, Yan F, Monson EE, Kopelman R (2003) Room-temperature preparation and characterization of poly (ethylene glycol)-coated silica nanoparticles for biomedical applications. J Biomed Mater Res 66:870–879
Zhu XY, Jun Y, Staarup DR, Major RC, Danielson S, Boiadjev SV, Gladfelter WL, Bunker BC, Guo A (2001) Grafting of high-density poly(ethylene glycol) monolayers on Si(111). Langmuir 17(25):7798–7803
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The authors thank Mr. A. Skripka for the helpful discussions.
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This study was funded by Fondazione Cariverona, Verona Nanomedicine Initiative and Italian Minister of Health RF-2010-2305526.
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Electronic Supplementary Information (ESI) available: [Details of the experimental procedure for the synthesis of mPEG5000-silane and mPEG550-silane, bare and pegylated SNPs and FSNPs; cell cultures; XRPD pattern and high magnification SEM image of bare SNPs (S), SEM micrographs of samples S25a, S8b, and S50a50b; FTIR spectra, DLS and z-potential analysis of the three series of samples; molybdate test calibration curve; PL-PLE spectra of FSNPs; SDS-PAGE of selected samples after soaking in BSA and human serum; semi-quantitative analysis of the serum protein adsorption on the SNP surface; cell viability tests on fibroblasts and RAW264.7 macrophages before and after BSA soaking at 24 h and 48 h; cell viability tests of bare and pegylated FSNPs on RAW 264.7 macrophages; raw flow cytometry data for the macrophages uptake of FSNPs]. (DOCX 4.70 mb)
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Glorani, G., Marin, R., Canton, P. et al. Pegylated silica nanoparticles: cytotoxicity and macrophage uptake. J Nanopart Res 19, 294 (2017). https://doi.org/10.1007/s11051-017-3964-x
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DOI: https://doi.org/10.1007/s11051-017-3964-x