Skip to main content
Log in

Synthesis, characterization, and in vitro biological evaluation of highly stable diversely functionalized superparamagnetic iron oxide nanoparticles

  • Research Paper
  • Published:
Journal of Nanoparticle Research Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  • 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

    Article  Google Scholar 

  • Bee A, Massart R, Neveu S (1995) Synthesis of very fine maghemite particles. J Magn Magn Mater 149:6–9

    Article  CAS  Google Scholar 

  • Bulte JWM, Kraitchman DL (2004) Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed 17:484–499

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • Chithrani BD, Ghazani AA, Chan WCW (2006) Determining the size, shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett 6:662–668

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • Dilnawaz F, Singh A, Mohanty C, Sahoo SK (2010) Dual drug loaded superparamagnetic iron oxide nanoparticles for targeted cancer therapy. Biomaterials 31:3694–3706

    Article  CAS  Google Scholar 

  • Flory PJ (1953) Principles of polymer chemistry. Cornell University Press, Ithaca, NY

    Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Kast CE, Schnürch AB (2001) Thiolated polymers-thiomers: development, in vitro evaluation of chitosan–thioglycolic acid conjugates. Biomaterials 22:2345–2352

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • Li GY, Jiang YR, Huang Kl, Ding P, Chen J (2008) Preparation, properties of magnetic Fe3O4–chitosan nanoparticles. J Alloys Compd 466:451–456

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • Mohapatra S, Pramanik P (2009) Synthesis and stability of functionalized iron oxide nanoparticles using organophosphorus coupling agents. Colloids Surf A 339:35–42

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Ravi Kumar MNV, Muzzarelli RAA, Muzzarelli C, Sashiwa H, Domb AJ (2004) Chitosan chemistry and pharmaceutical perspectives. Chem Rev 104:6017–6084

    Article  Google Scholar 

  • Schnürch AB, Scholler S, Biebel RG (2000) Development of controlled drug release systems based on thiolated polymers. J Control Release 66:39–48

    Article  Google Scholar 

  • Schnürch AB, Hornof M, Guggi D (2004) Thiolated chitosans. Eur J Pharmacol Biopharm 57:9–17

    Article  Google Scholar 

  • Shen T, Weissleder R, Papisov M, Bogdanov A, Brady TJ (1993) Monocrystalline iron-oxide nanocompounds (MION) physicochemical properties. Magn Reson Med 29:599–604

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Smaihi M, Gavilan E, Durand J, Valtchev VP (2004) Colloidal functionalized calcined zeolite nanocrystals. J Mater Chem 14:1347–1351

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Weissleder R, Bogdanov A, Neuwelt EA, Papisov M (1995) Long-circulating iron oxides for MR imaging. Adv Drug Delivery Rev 16:321–334

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Yi H, Wu LQ, Bentley WE, Ghodssi R, Rubloff GW, Culver JN, Payne GF (2005) Biofabrication with chitosan. Biomacromolecules 6(6):2881–2894

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Zhang Y, Kohler N, Zhang M (2002) Surface modification of superparamagnetic magnetite nanoparticles and their intracellular uptake. Biomaterials 23:1553–1561

    Article  CAS  Google Scholar 

  • Zhu A, Yuan L, Liao T (2008) Suspension of Fe3O4 nanoparticles stabilized by chitosan, o-carboxymethylchitosan. Int J Pharm 350:361–368

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge IIT Kharagpur and CSIR, New Delhi for providing financial support for this work.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Panchanan Pramanik.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11051-011-0362-7

Keywords

Navigation