Abstract
The nanoparticles containing thermosensitive and magnetic properties were investigated for their potential use as a novel drug carrier for targeted and controlled release drug delivery system. These thermosensitive and magnetic nanoparticles were prepared by grafting thermosensitive poly (N-isopropylacrylamide) (PNIPAM) on the surface of silica (SiO2)-coated Fe3O4 nanoparticles with the particle size of 18.8 ± 1.6 nm. Adsorption and desorption behavior of bovine serum albumin (BSA) on the surface of PNIPAM-grafted SiO2/Fe3O4 nanoparticles was studied, and the results indicated that these nanoparticles were able to absorb protein at temperature above the lower critical solution temperature (LCST) and to be desorbed below the LCST. Cytotoxicity studies conducted on Chinese hamster ovary (CHO-K1) cells using methyl tetrazolium (MTT) assays revealed that cell viability of 1 mg/mL PNIPAM-grafted nanoparticles was slightly decreased after 24 h of incubation as compared to the lower concentration of nanoparticles. Furthermore, the concentration of 0.5 mg/mL PNIPAM-grafted nanoparticles was totally biocompatible for 48 h, but had low cytotoxicity after 72 h of incubation. These PNIPAM-grafted nanoparticles did not induce morphological change in their cellularity after exposure for 24 and 108 h. These results demonstrate that PNIPAM-grafted nanoparticles are biocompatible and have potential use as drug carriers.
Similar content being viewed by others
References
Alexiou C, Schmidt A, Klein R, Hulin P, Bergemann C, Arnold W (2002) Magnetic drug targeting: biodistribution and dependency on magnetic field strength. J Magn Magn Mater 252:363–366
Chang Y, Su ZX (2002) Preparation and characterization of thermosensitive magnetic particles. Mater Sci Eng A Struct Mater Prop Microstruct Process 333(1–2):155–159
Cory AH, Owen TC, Barltrop JA, Cory JG (1991) Use of an aqueous soluble tetrazolium/formazan assay for cell growth assays in culture. Cancer Commun 3(7):207–212
Deng Y-H, Wang C–C, Hu J-H, Yang W-L, Fu S-K (2005) Investigation of formation of silica-coated magnetite nanoparticles via sol–gel approach. Colloids Surf A Physicochem Eng Asp 262(1–3):87–93
Di Virgilio AL, Reigosa M, Arnal PM, de Mele MFL (2010) Comparative study of the cytotoxic and genotoxic effects of titanium oxide and aluminium oxide nanoparticles in Chinese hamster ovary (cho-k1) cells. J Hazard Mater 177(1–3):711–718. doi:10.1016/j.jhazmat.2009.12.089
Ding XB, Sun ZH, Zhang WC, Peng YX, Wan GX, Jiang YY (2000) Adsorption/desorption of protein on magnetic particles covered by thermosensitive polymers. J Appl Polym Sci 77(13):2915–2920
Duracher D, Veyret R, Elaissari A, Pichot C (2004) Adsorption of bovine serum albumin protein onto amino-containing thermosensitive core–shell latexes. Polym Int 53(5):618–626. doi:10.1002/pi.1441
Eeckman F, Amighi K, Moes AJ (2001) Effect of some physiological and non-physiological compounds on the phase transition temperature of thermoresponsive polymers intended for oral controlled-drug delivery. Int J Pharm 222(2):259–270
Fan L, Wu H, Zhang H, Li F, Yang T-h, Gu C-h, Yang Q (2008) Novel super pH-sensitive nanoparticles responsive to tumor extracellular pH. Carbohydr Polym 73(3):390–400
Fisichella M, Dabboue H, Bhattacharyya S, Saboungi M-L, Salvetat J-P, Hevor T, Guerin M (2009) Mesoporous silica nanoparticles enhance MTT formazan exocytosis in hela cells and astrocytes. Toxicol In Vitro 23(4):697–703
Gelbrich T, Feyen M, Schmidt AM (2006) Magnetic thermoresponsive core–shell nanoparticles. Macromolecules 39(9):3469–3472. doi:10.1021/ma060006u
Gil ES, Hudson SM (2004) Stimuli-responsive polymers and their bioconjugates. Prog Polym Sci 29(12):1173–1222
Huang FK, Chen WC, Lai SF, Liu CJ, Wang CL, Wang CH, Chen HH, Hua TE, Cheng YY, Wu MK, Hwu Y, Yang CS, Margaritondo G (2010) Enhancement of irradiation effects on cancer cells by cross-linked dextran-coated iron oxide (clio) nanoparticles. Phys Med Biol 55(2):469–482. doi:10.1088/0031-9155/55/2/009
Huo D, Li Y, Qian Q, Kobayashi T (2006) Temperature–pH sensitivity of bovine serum albumin protein-microgels based on cross-linked poly(N-isopropylacrylamide-co-acrylic acid). Colloids Surf B Biointerfaces 50(1):36–42. doi:10.1016/j.colsurfb.2006.03.020
Hussain S, Boland S, Baeza-Squiban A, Hamel R, Thomassen LCJ, Martens JA, Billon-Galland MA, Fleury-Feith J, Moisan F, Pairon J-C, Marano F (2009) Oxidative stress and proinflammatory effects of carbon black and titanium dioxide nanoparticles: role of particle surface area and internalized amount. Toxicology 260(1–3):142–149
Kawaguchi H, Kawahara M, Yaguchi N, Hoshino F, Ohtsuka Y (1988) Hydrogel microspheres. 1. Preparation of monodisperse hydrogel microspheres of sub-micron or micron size. Polym J 20(10):903–909
Kohler N, Sun C, Wang J, Zhang MQ (2005) Methotrexate-modified superparamagnetic nanoparticles and their intracellular uptake into human cancer cells. Langmuir 21(19):8858–8864. doi:10.1021/la0503451
Lee WK, Ko JS, Kim HM (2002) Effect of electrostatic interaction on the adsorption of globular proteins on octacalcium phosphate crystal film. J Colloid Interface Sci 246(1):70–77. doi:10.1006/jcis.2001.8026
Lien YH, Wu TM (2008) Preparation and characterization of thermosensitive polymers grafted onto silica-coated iron oxide nanoparticles. J Colloid Interface Sci 326(2):517–521. doi:10.1016/j.jcis.2008.06.020
Lu Y, Mei Y, Ballauff M, Drechsler M (2006) Thermosensitive core–shell particles as carrier systems for metallic nanoparticles. J Phys Chem B 110(9):3930–3937. doi:10.1021/jp057149n
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. doi:10.1016/0022-1759(83)90303-4
Muller-Schulte D, Schmitz-Rode T (2006) Thermosensitive magnetic polymer particles as contactless controllable drug carriers. J Magn Magn Mater 302(1):267–271. doi:10.1016/j.jmmm.2005.05.043
Osswald J, Fehr KT (2006) FTIR spectroscopic study on liquid silica solutions and nanoscale particle size determination. J Mater Sci 41(5):1335–1339. doi:10.1007/s10853-006-7327-8
Piskareva O, Clynes M, Barron N (2007) Detection and cloning of Line-1 elements in CHO cells. Cytotechnology 53(1–3):75–80. doi:10.1007/s10616-007-9051-x
Rubio-Retama J, Zafeiropoulos NE, Serafinelli C, Rojas-Reyna R, Voit B, Cabarcos EL, Stamm M (2007) Synthesis and characterization of thermosensitive PNIPAM microgels covered with superparamagnetic gamma-Fe2O3 nanoparticles. Langmuir 23(20):10280–10285. doi:10.1021/la7009594
Schonhoff M, Larsson A, Welzel PB, Kuckling D (2002) Thermoreversible polymers adsorbed to colloidal silica: A H-1NMR and DSC study of the phase transition in confined geometry. J Phys Chem B 106(32):7800–7808. doi:10.1021/jp015538l
Shamim N, Hong L, Hidajat K, Uddin MS (2006) Thermosensitive-polymer-coated magnetic nanoparticles: adsorption and desorption of bovine serum albumin. J Colloid Interface Sci 304(1):1–8
Shamim N, Hong L, Hidajat K, Uddin MS (2007) Thermosensitive polymer coated nanomagnetic particles for separation of bio-molecules. Sep Purif Technol 53(2):164–170. doi:10.1016/j.seppur.2006.06.021
Shikano N, Nakajima S, Kotani T, Oqura M, Saqara J, Iwamura Y, Yoshimoto M, Kubota N, Ishikawa N, Kawai K (2007) Transport of d-[1-14C]-amino acids into Chinese hamster ovary (CHO-K1) cells: implications for use of labeled d-amino acids as molecular imaging agents. Nucl Med Biol 34(6):659–665. doi:10.1016/j.nucmedbio.2007.05.001
Stöber W, Fink A (1968) Controlled growth of monodisperse silica spheres in the micron size range. J Colloid Interface Sci 26(1):62–69
Takezawa T, Mori Y, Yoshizato K (1990) Cell culture on a thermoresponsive polymer surface. Biotechnology (NY) 8(9):854–856. doi:10.1038/nbt0990-854
Wadajkar AS, Koppolu B, Rahimi M, Nguyen KT (2009) Cytotoxic evaluation of n-isopropylacrylamide monomers and temperature-sensitive poly(n-isopropylacrylamide) nanoparticles. J Nanopart Res 11(6):1375–1382. doi:10.1007/s11051-008-9526-5
Wang SX, Zhou Y, Sun WT (2009) Preparation and characterization of antifouling thermosensitive magnetic nanoparticles for applications in biomedicine. Mater Sci Eng C Biomim Supramol Syst 29(4):1196–1200. doi:10.1016/j.msec.2008.10.007
Wang CW, Wang J, Gao W, Jiao JQ, Feng HJ, Liu X, Chen LP (2010a) One-pot preparation of thermoresponsive silica-poly(n-isopropylacrylamide) nanocomposite particles in supercritical carbon dioxide. J Colloid Interface Sci 343(1):141–148. doi:10.1016/j.jcis.2009.11.005
Wang P, He J, Wang PN, Chen JY (2010b) Poly (N-isopropylacrylamide)-coated multifunctional nanoparticles for cell tracking. Photomed Laser Surg 28(2):201–205. doi:10.1089/pho.2009.2546
Wu TM, Yen SJ, Chen EC, Sung TW, Chiang RK (2007) Conducting and magnetic behaviors of monodispersed iron oxide/polypyrrole nanocomposites synthesized by in situ chemical oxidative polymerization. J Polym Sci Polym Chem 45(20):4647–4655. doi:10.1002/pola.22211
Yi DK, Lee SS, Papaefthymiou GC, Ying JY (2006) Nanoparticle architectures templated by SiO2/Fe2O3 nanocomposites. Chem Mater 18(3):614–619. doi:10.1021/cm0512979
Zhang K, Fang H, Chen Z, Taylor JA, Wooley KL (2008) Shape effects of nanoparticles conjugated with cell-penetrating peptides (HIV Tat PTD) on CHO cell uptake. Bioconjug Chem 19(9):1880–1887. doi:10.1021/bc800160b
Zhou Y, Jia Xe, Tan L, Xie Q, Lei L, Yao S (2010) Magnetically enhanced cytotoxicity of paramagnetic selenium–ferroferric oxide nanocomposites on human osteoblast-like mg-63 cells. Biosens Bioelectron 25(5):1116–1121
Acknowledgments
The financial support provided by National Science Council through the project NSC96-2221-E-005-049 is greatly appreciated.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lien, YH., Wu, TM., Wu, JH. et al. Cytotoxicity and drug release behavior of PNIPAM grafted on silica-coated iron oxide nanoparticles. J Nanopart Res 13, 5065–5075 (2011). https://doi.org/10.1007/s11051-011-0487-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11051-011-0487-8