Abstract
In this study, we evaluated the combined effect of a known toxic molecule, cisplatin, in combination with relatively nontoxic nanoparticles, amorphous fumed silica, on chondrocyte cells. Cisplatin was attached to silica nanoparticles using aminopropyltriethoxy silane as a linker molecule, and characterized in terms of size, shape, specific surface area, as well as the dissolution of cisplatin from the silica surface. The primary particle diameter of the as-received silica nanoparticles ranged from 7.1 to 61 nm, estimated from measurements of specific surface area, and the primary particles were aggregated. The effects of cisplatin-functionalized silica particles with different specific surface areas (41, 85, 202, 237, and 297 m2/g) were compared in vitro on chondrocytes, the parenchymal cell of hyaline cartilage. The results show that adverse effects on cell function, as evidenced by reduced metabolic activity measured by the MTT assay and increased membrane permeability observed using the Live/Dead stain, can be correlated with specific surface area of the silica. Cisplatin-functionalized silica nanoparticles with the highest specific surface area incited the greatest response, which was almost equivalent to that induced by free cisplatin. This result suggests the importance of particle specific surface area in interactions between cells and surface-functionalized nanomaterials.
Similar content being viewed by others
References
Borum L, Wilson OC (2003) Surface modification of hydroxyapatite. Part II. Silica. Biomaterials 24(21):3681–3688
Boyan BD, Schwartz Z, Hambleton JC (1993) Response of bone and cartilage cells to biomaterials in vivo and in vitro. J Oral Implantol 19(2):116–122 (discussion 136–137)
Cepeda V, Fuertes MA, Castilla J, Alonso C, Quevedo C, Perez JM (2007) Biochemical mechanisms of cisplatin cytotoxicity. Anticancer Agents Med Chem 7(1):3–18
Chang JS, Chang KLB, Hwang DF, Kong ZL (2007) In vitro cytotoxicitiy of silica nanoparticles at high concentrations strongly depends on the metabolic activity type of the cell line. Environ Sci Technol 41(6):2064–2068
De Jong WH, Borm PJA (2008) Drug delivery and nanoparticles: applications and hazards. Int J Nanomedicine 3(2):133–149
Duffin R, Tran L, Brown D, Stone V, Donaldson K (2007) Proinflammogenic effects of low-toxicity and metal nanoparticles in vivo and in vitro: highlighting the role of particle surface area and surface reactivity. Inhal Toxicol 19(10):849–856
Franks A (1987) Nanotechnology. J Phys E 20(12):1442–1451
Fripiat JJ (1982) Silanol groups and properties of silica surfaces. ACS Symp Ser 194:165–184
Fujiwara K, Suematsu H, Kiyomiya E, Aoki M, Sato M, Moritoki N (2008) Size-dependent toxicity of silica nano-particles to Chlorella kessleri. J Environ Sci Health A 43(10):1167–1173
Garcon G, Gosset P, Garry S, Marez T, Hannothiaux MH, Shirali P (2001) Pulmonary induction of proinflammatory mediators following the rat exposure to benzo(a)pyrene-coated onto Fe2O3 particles. Toxicol Lett 121(2):107–117
Garry S, Nesslany F, Aliouat E, Haguenoer JM, Marzin D (2004) Hematite (Fe2O3) acts by oxydative stress and potentiates benzo[a]pyrene genotoxicity. Mutat Res 563(2):117–129
Gerstner E (2003) Electronics: nanotechnology goes large. Nature 425(6955):244
Guthrie GD Jr (1997) Mineral properties and their contributions to particle toxicity. Environ Health Perspect 105(Suppl 5):1003–1011
Hannah W, Thompson PB (2008) Nanotechnology, risk and the environment: a review. J Environ Monit 10(3):291–300
Iler RK (1979) The chemistry of silica: solubility, polymerization, colloid and surface properties, and biochemistry. Wiley, New York, xxiv, 866 pp
Katz HS, Milewski JV (1987) Handbook of fillers for plastics. Van Nostrand Reinhold Co, New York
Kim JK, Anderson J, Jun HW, Repka MA, Jo S (2009) Self-assembling peptide amphiphile-based nanofiber gel for bioresponsive cisplatin delivery. Mol Pharm 6(3):978–985
Koga K, Kaji A, Hirosaki K, Hata Y, Ogura T, Fujishita O, Shintani K (2006) Cytotoxic evaluation of cubic boron nitride in human origin cultured cells. Toxicol In Vitro 20(8):1370–1377
Koo OM, Rubinstein I, Onyuksel H (2005) Role of nanotechnology in targeted drug delivery and imaging: a concise review. Nanomedicine 1(3):193–212
Kovacs AF, Cinatl J (2002) In vitro cytotoxic dose-relation of cisplatin and sodium thiosulphate in human tongue and oesophageal squamous carcinoma cell lines. J Craniomaxillofac Surg 30(1):54–58
Limbach LK, Wick P, Manser P, Grass RN, Bruinink A, Stark WJ (2007) Exposure of engineered nanoparticles to human lung epithelial cells: influence of chemical composition and catalytic activity on oxidative stress. Environ Sci Technol 41:4158–4163
Lin W, Huang YW, Zhou XD, Ma Y (2006) In vitro toxicity of silica nanoparticles in human lung cancer cells. Toxicol Appl Pharmacol 217(3):252–259
Lippmann M, Yeates DB, Albert RE (1980) Deposition, retention, and clearance of inhaled particles. Br J Ind Med 37(4):337–362
Mathias J, Wannemacher G (1988) Basic characteristics and applications of Aerosil.30. The chemistry and physics of the Aerosil surface. J Colloid Interf Sci 125(1):61–68
Medina C, Santos-Martinez MJ, Radomski A, Corrigan OI, Radomski MW (2007) Nanoparticles: pharmacological and toxicological significance. Br J Pharmacol 150(5):552–558
Meijer C, van Luyn MJA, Nienhuis EF, Blom N, Mulder NH, de Vries EGE (2001) Ultrastructural morphology and localisation of cisplatin-induced platinum-DNA adducts in a cisplatin-sensitive and -resistant human small cell lung cancer cell line using electron microscopy. Biochem Pharmacol 61(5):573–578
Mitra A, Nan A, Line BR, Ghandehari H (2006) Nanocarriers for nuclear imaging and radiotherapy of cancer. Curr Pharm Des 12(36):4729–4749
Miura K, Goldstein RS, Pasino DA, Hook JB (1987) Cisplatin nephrotoxicity: role of filtration and tubular transport of cisplatin in isolated perfused kidneys. Toxicology 44(2):147–158
Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65(1–2):55–63
Oberdorster G (2000) Toxicology of ultrafine particles: in vivo studies. Philos Transact A 358(1775):2719–2740
Ohmori T, Morikage T, Sugimoto Y, Fujiwara Y, Kasahara K, Nishio K, Ohta S, Sasaki Y, Takahashi T, Saijo N (1993) The mechanism of the difference in cellular uptake of platinum derivatives in non-small cell lung cancer cell line (PC-14) and its cisplatin-resistant subline (PC-14/CDDP). Jpn J Cancer Res 84(1):83–92
Pandurangi RS, Seehra MS, Razzaboni BL, Bolsaitis P (1990) Surface and bulk infrared modes of crystalline and amorphous silica particles: a study of the relation of surface structure to cytotoxicity of respirable silica. Environ Health Perspect 86:327–336
Pham KN, Fullston D, Sagoe-Crentsil K (2007) Surface modification for stability of nano-sized silica colloids. J Colloid Interf Sci 315(1):123–127
Robson H, Anderson E, Eden OB, Isaksson O, Shalet S (1998) Chemotherapeutic agents used in the treatment of childhood malignancies have direct effects on growth plate chondrocyte proliferation. J Endocrinol 157(2):225–235
Setter N, Waser R (2000) Electroceramic materials. Acta Mater 48(1):151–178
Su WC, Chang SL, Chen TY, Chen JS, Tsao CJ (2000) Comparison of in vitro growth-inhibitory activity of carboplatin and cisplatin on leukemic cells and hematopoietic progenitors: the myelosuppressive activity of carboplatin may be greater than its antileukemic effect. Jpn J Clin Oncol 30(12):562–567
Warheit DB, Webb TR, Colvin VL, Reed KL, Sayes CM (2007) Pulmonary bioassay studies with nanoscale and fine-quartz particles in rats: toxicity is not dependent upon particle size but on surface characteristics. Toxicol Sci 95(1):270–280
Wurster DE, Taylor PW (1965) Dissolution rates. J Pharm Sci 54:169–175
Yoon DM, Hawkins EC, Francke-Carroll S, Fisher JP (2007) Effect of construct properties on encapsulated chondrocyte expression of insulin-like growth factor-1. Biomaterials 28(2):299–306
Acknowledgments
The authors acknowledge with thanks Dr. Wen An Chiou, (NISPLab, College Park, University of Maryland), for assistance in TEM, and Tim Maugel, (Laboratory for Biological Ultrastructure, University of Maryland) for assistance in thin sectioning. The authors also thank Dr. Karen Gaskell (Department of Chemistry and Biochemistry, University of Maryland) for assistance with XPS measurements. We acknowledge the support of the Maryland NanoCenter and its NispLab. The NispLab and XPS facilities are supported in part by the National Science Foundation as MRSEC Shared Experimental Facilities. This study was supported by National Institute of Standards and Technology (NIST) (grant no—60NANB6D6169).
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Bhowmick, T.K., Yoon, D., Patel, M. et al. In vitro effects of cisplatin-functionalized silica nanoparticles on chondrocytes. J Nanopart Res 12, 2757–2770 (2010). https://doi.org/10.1007/s11051-010-9849-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11051-010-9849-x