Abstract
Purpose
Early stage diseases diagnosed using magnetic resonance imaging (MRI) techniques is of high global interest as a potent noninvasive modality. MRI contrast agents are improved through modifications in structural and physicochemical properties of the applied nanoprobes. But, the potential toxic effects of nanoprobes upon exposure to biological systems are still a major concern.
Procedure
In this study, the acute toxicity of glycosylated Gd3+-based silica mesoporous nanospheres (GSNs) as a MRI contrast agent was evaluated in Balb/c mice. In order to evaluate in vivo toxicity of GSN, preclinical studies, daily weight monitoring, hematological/blood chemistry tests, and histological assessment were conducted. Magnetic resonance relaxivities of GSN was determined using a MRI scanner.
Results
The obtained results suggest that in vivo toxicity of GSN was mostly influenced by nanoparticle surface area, functionality, and nanoparticle zeta potential. The maximum tolerated dose (MTD) increased in the following order: mesoporous silica nanospheres (MSNs) at 1 mg/mice < GSN (aspect ratio 1, 2, 8) at 40 mg/mice. The results also indicate GSN, one of the best cell imaging contrast agent, which does not show any significant toxicity on multiple vital organs following injection of 20 mg/mice, while a significant T1-weighted enhancement was observed in whole body of a Balb/c mice 15 min postinjection of (5 μmol/kg) of body weight of GSN.
Conclusions
These results shed light on the functionality of MSNs to minimize in vivo toxicity. Also, glyconanoprobe can be beneficially used for nanomedicine and cellular imaging applications without any significant toxicity.
Similar content being viewed by others
References
Taylor KML, Kim JS, Rieter WJ et al (2008) Mesoporous silica nanospheres as highly efficient MRI contrast agents. J Am Chem Soc 130:2154–2155
Bulte JWM (2004) The chemistry of contrast agents in medical magnetic resonance imaging. NMR Biomed 17(4):240–262
Ananta SJ, Godin B, Sethi R et al (2010) Geometrical confinement of gadolinium-based contrast agents in nanoporous particles enhances T1 contrast. Nat Nanotechnol 5(11):815–821
Slowing II, Vivero-Escoto JL, Wu C-W, Lin VSY (2008) Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers. Adv Drug Deliv Rev 60:1278–1288
He Q, Shi J (2011) Mesoporous silica nanoparticle based nano drug delivery systems: synthesis, controlled drug release and delivery, pharmacokinetics and biocompatibility. J Mater Chem 21:5845–5855
Vivero-Escoto JL, Slowing II, Trewyn BG et al (2010) Mesoporous silica nanoparticles for intracellular controlled drug delivery. Small 6:1952–1967
Lu J, Liong M, Li Z et al (2010) Biocompatibility, biodistribution, and drug-delivery efficiency of mesoporous silica nanoparticles for cancer therapy in animals. Small 6:1794–1805
Li L, Tang F, Liu H et al (2010) In vivo delivery of silica nanorattle encapsulated docetaxel for liver cancer therapy with low toxicity and high efficacy. ACS Nano 4:6874–6882
Nan A, Bai X, Son SJ et al (2008) Cellular uptake and cytotoxicity of silica nanotubes. Nano Lett 8:2150–2154
Tsai CP, Hung Y, Chou YH et al (2008) High-contrast paramagnetic fluorescent mesoporous silica nanorods as a multifunctional cell-imaging probe. Small 4:186–191
Mehravi B, Ahmadi M, Amanlou M et al (2013) Conjugation of glucosamine on Gd3+ based nanoporous silica using heterobifunctional crosslinker (ANB-NOS) for cancer cell imaging. Int J Nanomedicine 8:3383–3394
Mehravi B, Ahmadi M, Amanlou M et al (2013) Cellular uptake and imaging studies of glycosylated nilica nanoprobe (GSN) in human Colon adenocarcinoma (HT 29 cell line). Int J Nanomedicine 8:3209–3216
Mehravi B, Shafiee AM, Damercheli M et al (2014) Breast cancer cells imaging by targeting methionine transporters with gadolinium-based nanoprobe. Mol Imaging Biol 16(4):519–528
Venkatesan N, Yoshimitsu J, Ito Y et al (2005) Liquid filled nanoparticles as a drug delivery tool for protein therapeutics. Biomaterials 26:7154–7163
Bharali DJ, Klejbor I, Stachowiak EK et al (2005) Organically modified silica nanoparticles: a nonviral vector for in vivo gene delivery and expression in the brain. Proc Natl Acad Sci 102:11539–11544
Gemeinhart RA, Luo D, Saltzman WM et al (2005) Cellular fate of a modular DNA delivery system mediated by silica nanoparticles. Biotechnol Prog 21:532–537
Zhang FF, Wan Q, Li CX et al (2004) Simultaneous assay of glucose, lactate, L-glutamate and hypoxanthine levels in a rat striatum using enzyme electrodes based on neutral red-doped silica nanoparticles. Anal Bioanal Chem 380:637–642
Qhobosheane M, Santra S, Zhang P et al (2001) Biochemically functionalized silica nanoparticles. Analyst 126:1274–1278
Chen J, Dong X, Zhao J et al (2009) In vivo acute toxicity of titanium dioxide nanoparticles to mice after intraperitoneal injection. J Appl Toxicol 29:330–337
Endemann DH, Schiffrin EL et al (2004) Endothelial dysfunction. J Am Soc 15:1983–1992
Liu X, Sun J et al (2010) Endothelial cells dysfunction induced by silica nanoparticles through oxidative stress via JNK/P53 and NF-κB pathways. Biomaterials 31:8198–8209
Hainfeld JF, Slatkin DN, Focella TM et al (2006) Gold nanoparticles: a new X-ray contrast agent. Br J Radiol 79:248–253
Petushkov A, Intra J, Graham JB et al (2009) Effect of crystal size and surface functionalization on the cytotoxicity of silicalite-1 nanoparticles. Chem Res Toxicol 22:1359–1368
Waters KM, Masiello LM, Zangar RC et al (2009) Macrophage responses to silica nanoparticles are highly conserved across particle sizes. Toxicol Sci 107:553–569
Oberdorster G, Oberdorster E, Oberdorster J et al (2005) Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ. Health Perspect 113:823–839
He Q, Zhang Z, Gao F et al (2011) In vivo biodistribution and urinary excretion of mesoporous silica nanoparticles: effects of particle size and pegylation. Small 7:271–280
Galagudza MM, Korolev DV, Sonin DL et al (2010) Targeted drug delivery into reversibly injured myocardium with silica nanoparticles: surface functionalization, natural biodistribution, and acute toxicity. Int J Nanomedicine 5:231–237
Zhao Y, Sun X, Zhang G et al (2011) Interaction of mesoporous silica nanoparticles with human red blood cell membranes: size and surface effects. ACS Nano 5:1366–1375
Yu T, Malugin A, Ghandehari H (2011) Impact of silica nanoparticle design on cellular toxicity and hemolytic activity. ACS Nano 5:5717–5728
Yu T, Greish K, McGill LD et al (2012) Influence of geometry, porosity, and surface characteristics of silica nanoparticles on acute toxicity: their vasculature effect and tolerance threshold. ACS Nano 6:2289–2301
Oberdörster G, Oberdörster E, Oberdörster J (2005) Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113:823–839
Krug HF, Wick P et al (2011) Nanotoxicology: an interdisciplinary challenge. Angew Chem Int Ed 50:1260–1278
Acknowledgements
We would like to acknowledge Dr. Abazar Hosseini at Iran University of Medical Sciences for advising on histological sample analysis. Furthermore, financial support was provided by Iran University of Medical Sciences.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of Interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Mehravi, B., Alizadeh, A.M., Khodayari, S. et al. Acute Toxicity Evaluation of Glycosylated Gd3+-Based Silica Nanoprobe. Mol Imaging Biol 19, 522–530 (2017). https://doi.org/10.1007/s11307-016-1025-y
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11307-016-1025-y