Abstract
In this article, we report the design and synthesis of a series of well-dispersed superparamagnetic iron oxide nanoparticles (SPIONs) using chitosan as a surface modifying agent to develop a potential T 2 contrast probe for magnetic resonance imaging (MRI). The amine, carboxyl, hydroxyl, and thiol functionalities were introduced on chitosan-coated magnetic probe via simple reactions with small reactive organic molecules to afford a series of biofunctionalized nanoparticles. Physico-chemical characterizations of these functionalized nanoparticles were performed by TEM, XRD, DLS, FTIR, and VSM. The colloidal stability of these functionalized iron oxide nanoparticles was investigated in presence of phosphate buffer saline, high salt concentrations and different cell media for 1 week. MRI analysis of human cervical carcinoma (HeLa) cell lines treated with nanoparticles elucidated that the amine-functionalized nanoparticles exhibited higher amount of signal darkening and lower T 2 relaxation in comparison to the others. The cellular internalization efficacy of these functionalized SPIONs was also investigated with HeLa cancer cell line by magnetically activated cell sorting (MACS) and fluorescence microscopy and results established selectively higher internalization efficacy of amine-functionalized nanoparticles to cancer cells. These positive attributes demonstrated that these nanoconjugates can be used as a promising platform for further in vitro and in vivo biological evaluations.
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Aryal S, Remant BKC, Dharmaraj N, Bhattarai N, Kim CH, Kim HY (2006) Spectroscopic identification of S-Au interaction in cysteine capped gold nanoparticles. Spectrochim Acta A 63:160–163
Bee A, Massart R, Neveu S (1995) Synthesis of very fine maghemite particles. J Magn Magn Mater 149:6–9
Bulte JWM, Kraitchman DL (2004) Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed 17:484–499
Chang YC, Chen DH (2005) Adsorption kinetics and thermodynamics of acid dyes on a carboxymethylated chitosan-conjugated magnetic nano-adsorbent. Macromol Biosci 5:254–261
Chen ZP, Xu RZ, Zhang Y, Gu N (2008) Effects of proteins from culture medium on surface property of silanes-functionalized magnetic nanoparticles. Nanoscale Res Lett 4:204–209
Chithrani BD, Ghazani AA, Chan WCW (2006) Determining the size, shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett 6:662–668
Das M, Mishra D, Maiti TK, Basak A, Pramanik P (2008) Bio-functionalization of magnetite nanoparticles using an aminophosphonic acid coupling agent: new, ultradispersed, iron-oxide folate nanoconjugates for cancer-specific targeting. Nanotechnology 19:415101–415115
Das M, Dhak P, Gupta S, Mishra D, Maiti TK, Basak A, Pramanik P (2010) Highly biocompatible and water-dispersible, amine functionalized magnetite nanoparticles, prepared by a low temperature, air-assisted polyol process: a new platform for bio-separation and diagnostics. Nanotechnology 21:125103–125115
Dilnawaz F, Singh A, Mohanty C, Sahoo SK (2010) Dual drug loaded superparamagnetic iron oxide nanoparticles for targeted cancer therapy. Biomaterials 31:3694–3706
Flory PJ (1953) Principles of polymer chemistry. Cornell University Press, Ithaca, NY
Gu H, Xu K, Xu C, Xu B (2006) Biofunctional magnetic nanoparticles for protein separation and pathogen detection. Chem Commun 941–949
Hong RY, Feng B, Chen LL, Liu GH, Li HZ, Zheng Y, Wei DG (2008) Synthesis characterization, MRI application of dextran-coated Fe3O4 magnetic nanoparticles. Biochem Eng J 42:290–300
Hu F, Wei L, Zhou Z, Ran Y, Li Z, Gao M (2006) Preparation of biocompatible magnetite nanocrystals for in vivo magnetic resonance detection of cancer. Adv. Mater 18:2553–2556
Huang HC, Chang PY, Chang K, Chen CY, Lin CW, Chen JH, Mou CY (2009) Formulation of novel lipid-coated magnetic nanoparticles as the probe for in vivo imaging. J Biomed Sci 16:86
Jun YW, Lee JH, Cheon J (2008) Chemical design of nanoparticle probes for high-performance magnetic resonance imaging. Angew Chem Int Ed 47:5122–5135
Kast CE, Schnürch AB (2001) Thiolated polymers-thiomers: development, in vitro evaluation of chitosan–thioglycolic acid conjugates. Biomaterials 22:2345–2352
Kawaguchi T, Hanaichi T, Hasegawa M, Maruno S (2001) Dextran-magnetite complex: conformation of dextran chains, stability of solution. J Mater Sci Mater Med 12:121–127
Kim EH, Lee HS, Kwak BK, Kim BK (2005) Synthesis of ferrofluid with magnetic nanoparticles by sonochemical method for MRI contrast agent. J Magn Magn Mater 289:328–330
Lee HS, Kim EH, Shao HP, Kwak BK (2005) Synthesis of spio-chitosan microspheres for MRI-detectable embolotherapy. J Magn Magn Mater 293:102–105
Levy FE, Andry MC, Levy MC (1993) Determination of free amino group content of serum albumin microcapsules using trinitrobenzenesulfonic acid: effect of variations in polycondensation pH. Int J Pharm 96:85–90
Li GY, Jiang YR, Huang Kl, Ding P, Chen J (2008) Preparation, properties of magnetic Fe3O4–chitosan nanoparticles. J Alloys Compd 466:451–456
Lin H, Watanabe Y, Kimura M, Hanabusa K, Shirai H (2003) Preparation of magnetic poly(vinyl alcohol) (PVA) materials by in situ synthesis of magnetite in a PVA matrix. J Appl Polym Sci 87:1239–1247
Lin JJ, Chen JS, Huang SJ, Ko JH, Wang YM, Chen TL, Wang LF (2009) Folic acid–Pluronic F127 magnetic nanoparticle clusters for combined targeting, diagnosis, and therapy applications. Biomaterials 30:5114–5124
Ma Hl, Qi Xr, Maitani Y, Nagai T (2007) Preparation and characterization of superparamagnetic iron oxide nanoparticles stabilized by alginate. Int J Pharm 333:177–186
Marco MD, Guilbert I, Port M, Robic C, Couvreur P, Dubernet C (2007) Colloidal stability of ultrasmall superparamagnetic iron oxide (USPIO) particles with different coatings. Int J Pharm 331:197–203
Mohapatra S, Pramanik P (2009) Synthesis and stability of functionalized iron oxide nanoparticles using organophosphorus coupling agents. Colloids Surf A 339:35–42
Nath S, Kaittanis C, Vasanth R, Dalal NS, Perez JM (2009) Synthesis, magnetic characterization, and sensing applications of novel dextran-coated iron oxide nanorods. Chem Mater 21:1761–1767
Petri-Fink A, Steitz B, Finka A, Salaklang J, Hofmann H (2008) Effect of cell media on polymer coated superparamagnetic iron oxide nanoparticles (SPIONs): colloidal stability, cytotoxicity, and cellular uptake studies. Eur J Pharmacol Biopharm 68:129–137
Ravi Kumar MNV, Muzzarelli RAA, Muzzarelli C, Sashiwa H, Domb AJ (2004) Chitosan chemistry and pharmaceutical perspectives. Chem Rev 104:6017–6084
Schnürch AB, Scholler S, Biebel RG (2000) Development of controlled drug release systems based on thiolated polymers. J Control Release 66:39–48
Schnürch AB, Hornof M, Guggi D (2004) Thiolated chitosans. Eur J Pharmacol Biopharm 57:9–17
Shen T, Weissleder R, Papisov M, Bogdanov A, Brady TJ (1993) Monocrystalline iron-oxide nanocompounds (MION) physicochemical properties. Magn Reson Med 29:599–604
Shi XY, Wang SH, Swanson SD, Ge S, Cao ZY, Van Antwerp ME, Landmark KJ, Baker JR (2008) Dendrimer-functionalized shell-crosslinked iron oxide nanoparticles for in vivo magnetic resonance imaging of tumors. Adv Mater 20:1671–1678
Smaihi M, Gavilan E, Durand J, Valtchev VP (2004) Colloidal functionalized calcined zeolite nanocrystals. J Mater Chem 14:1347–1351
Sonvico F, Mornet S, Vasseur S, Dubernet C, Jaillard D, Degrouard J, Hoebeke J, Duguet E, Colombo P, Couvreur P (2005) Folate-conjugated iron oxide nanoparticles for solid tumor targeting as potential specific magnetic hyperthermia mediators: synthesis, physicochemical characterization, and in vitro experiments. Bioconjugate Chem 16:1181–1188
Tan H, Xue JM, Shuter B, Li X, Wang J (2010) Synthesis of PEOlated Fe3O4@SiO2 nanoparticles via bioinspired silification for magnetic resonance imaging. Adv Funct Mater 20:722–731
Veiseh O, Sun C, Gunn J, Kohler N, Gabikian P, Lee D, Bhattarai N, Ellenbogen R, Sze R, Hallahan A, Olson J, Zhang M (2005) Optical and MRI multifunctional nanoprobe for targeting gliomas. Nano Lett 5:1003–1008
Wang S, Zhou Y, Yang S, Ding B (2008) Growing hyperbranched polyglycerols on magnetic nanoparticles to resist nonspecific adsorption of proteins. Colloids Surf B 67:122–126
Weissleder R, Bogdanov A, Neuwelt EA, Papisov M (1995) Long-circulating iron oxides for MR imaging. Adv Drug Delivery Rev 16:321–334
Weissleder R, Moore A, Mahmood U, Bhorade R, Benveniste H, Chiocca EA, Basilion JP (2000) In vivo magnetic resonance imaging of transgene expression. Nat Med 6:351–354
Win KY, Feng S (2005) Effects of particle size, surface coating on cellular uptake of polymeric nanoparticles for oral delivery of anticancer drugs. Biomaterials 26:2713–2722
Yi H, Wu LQ, Bentley WE, Ghodssi R, Rubloff GW, Culver JN, Payne GF (2005) Biofabrication with chitosan. Biomacromolecules 6(6):2881–2894
Yin L, Ding J, He C, Cui L, Tang C, Yin C (2009) Drug permeability, mucoadhesion properties of thiolated trimethyl chitosan nanoparticles in oral insulin delivery. Biomaterials 30:5691–5700
Yuan JJ, Armes SP, Takabayashi Y, Prassides KC, Galembeck F, Lewis AL (2006) Synthesis of biocompatible poly[2-(methacryloyloxy)ethyl phosphorylcholine]-coated magnetite nanoparticles. Langmuir 22:10989–10993
Zhang Y, Kohler N, Zhang M (2002) Surface modification of superparamagnetic magnetite nanoparticles and their intracellular uptake. Biomaterials 23:1553–1561
Zhu A, Yuan L, Liao T (2008) Suspension of Fe3O4 nanoparticles stabilized by chitosan, o-carboxymethylchitosan. Int J Pharm 350:361–368
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The authors gratefully acknowledge IIT Kharagpur and CSIR, New Delhi for providing financial support for this work.
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Bhattacharya, D., Sahu, S.K., Banerjee, I. et al. Synthesis, characterization, and in vitro biological evaluation of highly stable diversely functionalized superparamagnetic iron oxide nanoparticles. J Nanopart Res 13, 4173–4188 (2011). https://doi.org/10.1007/s11051-011-0362-7
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DOI: https://doi.org/10.1007/s11051-011-0362-7