Maghemite (γ-Fe2O3) nanoparticles obtained through co-precipitation and oxidation were coated with heparin (Hep) to yield γ-Fe2O3@Hep, and subsequently with chitosan that was modified with different phenolic compounds, including gallic acid (CS-G), hydroquinone (CS-H), and phloroglucinol (CS-P), to yield γ-Fe2O3@Hep-CS-G, γ-Fe2O3@Hep-CS-H, and γ-Fe2O3@Hep-CS-P particles, respectively. Surface modification of the particles was analyzed by transmission electron microscopy, dynamic light scattering, attenuated total reflection Fourier transform infrared spectroscopy, and thermogravimetric analysis. Magnetic measurements indicated that the polymer coating does not affect the superparamagnetic character of the iron oxide core. However, magnetic saturation decreased with increasing thickness of the polymer coating. The antioxidant properties of the nanoparticles were analyzed using a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Cellular uptake and intracellular antioxidant activity of the particles were evaluated by an iron assay and flow cytometry, respectively, using L-929 and LN-229 cells. Compared to the control, the phenolic modification significantly reduced intracellular reactive oxygen species (ROS) levels to 35-56%, which was associated with a 6-8-times higher cellular uptake in L-929 cells and a 21-31-times higher cellular uptake in LN-229 cells. In contrast, γ-Fe2O3@Hep particles induced a 3.8-times and 14.9-times higher cellular uptake without inducing antioxidant activity. In conclusion, the high cellular uptake and the antioxidant properties associated with the phenolic moieties in the modified particles allow for a potential application in biomedical areas.

BioISI Biosystems and Integrative Sciences Faculdade de Ciências Universidade de Lisboa Lisboa 1749 016 Portugal

Department of Physiology and Pharmacology and Healthy Aging Research Center College of Medicine Chang Gung University Guishan Taoyuan 33302 Taiwan ROC

Institute of Macromolecular Chemistry Czech Academy of Sciences Heyrovského nám 2 Prague 6 162 06 Czech Republic

Physics Department University of Coimbra Coimbra 3004 516 Portugal

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Valko M, Leibfritz D, Moncol J, Cronin M T D, Mazur M, Telser J. Int J Biochem Cell Biol. 2007;39:44–84. doi: 10.1016/j.biocel.2006.07.001. PubMed DOI

Dröge W. Physiol Rev. 2002;82:47–95. doi: 10.1152/physrev.00018.2001. PubMed DOI

Nimse S B, Pal D. RSC Adv. 2015;5:27986–28006. doi: 10.1039/c4ra13315c. DOI

Dimitrios D. Trends Food Sci Technol. 2006;17:505–512. doi: 10.1016/j.tifs.2006.04.004. DOI

Pereira D, Valentão P, Pereira J, Andrade P. Molecules. 2009;14(6):2202–2211. doi: 10.3390/molecules14062202. DOI

Das D, Nath B C, Phukon P, Kalita A, Dolui S K. Colloids Surf, B. 2013;111:556–560. doi: 10.1016/j.colsurfb.2013.06.041. PubMed DOI

Nagajyothi P C, Cha S J, Yang I J, Sreekanth T V M, Kim K J, Shin H M. J Photochem Photobiol, B. 2015;146:10–17. doi: 10.1016/j.jphotobiol.2015.02.008. PubMed DOI

Caputo F, De Nicola M, Sienkiewicz A, Giovanetti A, Bejarano I, Licoccia S, Traversa E, Ghibelli L. Nanoscale. 2015;7:15643–15656. doi: 10.1039/c5nr03767k. PubMed DOI

Lee S S, Song W, Cho M, Puppala H L, Nguyen P, Zhu H, Segatori L, Colvin V L. ACS Nano. 2013;7:9693–9703. doi: 10.1021/nn4026806. PubMed DOI

Reddy N J, Nagoor Vali D, Rani M, Rani S S. Mater Sci Eng, C. 2014;34:115–122. doi: 10.1016/j.msec.2013.08.039. PubMed DOI

Paul S, Saikia J P, Samdarshi S K, Konwar B K. J Magn Magn Mater. 2009;321:3621–3623. doi: 10.1016/j.jmmm.2009.07.004. DOI

Kumar M N V R. React Funct Polym. 2000;46:1–27. doi: 10.1016/s1381-5148(00)00038-9. DOI

Xie M, Hu B, Wang Y, Zeng X. J Agric Food Chem. 2014;62:9128–9136. doi: 10.1021/jf503207s. PubMed DOI

Yen M-T, Yang J-H, Mau J-L. Carbohydr Polym. 2008;74:840–844. doi: 10.1016/j.carbpol.2008.05.003. DOI

Tomida H, Fujii T, Furutani N, Michihara A, Yasufuku T, Akasaki K, Maruyama T, Otagiri M, Gebicki J M, Anraku M. Carbohydr Res. 2009;344:1690–1696. doi: 10.1016/j.carres.2009.05.006. PubMed DOI

Oliver S, Vittorio O, Cirillo G, Boyer C. Polym Chem. 2016;7:1529–1544. doi: 10.1039/c5py01912e. DOI

Richardson J J, Cui J, Björnmalm M, Braunger J A, Ejima H, Caruso F. Chem Rev. 2016;116:14828–14867. doi: 10.1021/acs.chemrev.6b00627. PubMed DOI

López-Martínez L M, Santacruz-Ortega H, Navarro R-E, Sotelo-Mundo R R, González-Aguilar G A. PLoS One. 2015;10:No. e0140242. doi: 10.1371/journal.pone.0140242. PubMed DOI PMC

Arizmendi-Cotero D, Gómez-Espinosa R M, Dublán García O, Gómez-Vidales V, Dominguez-Lopez A. Carbohydr Polym. 2016;136:350–357. doi: 10.1016/j.carbpol.2015.09.037. PubMed DOI

Fedoseeva E N, Smirnova L A, Sorokina M A, Pastukhov M O. Russ J Appl Chem. 2006;79:845–849. doi: 10.1134/s1070427206050296. DOI

Pillai C K S, Paul W, Sharma C P. Prog Polym Sci. 2009;34:641–678. doi: 10.1016/j.progpolymsci.2009.04.001. DOI

Prior R L, Wu X, Schaich K. J Agric Food Chem. 2005;53:4290–4302. doi: 10.1021/jf0502698. PubMed DOI

Everette J D, Bryant Q M, Green A M, Abbey Y A, Wangila G W, Walker R B. J Agric Food Chem. 2010;58:8139–8144. doi: 10.1021/jf1005935. PubMed DOI PMC

Serna C J, Morales M P. Maghemite (γ-Fe2O3): A versatile magnetic colloidal material. In: Matijević E, Borkovec M, editors. Surface and Colloid Science. Boston, MA, U.S.A.: Springer; 2004. pp. 27–81. DOI

Nazari M, Ghasemi N, Maddah H, Motlagh M M. J Nanostruct Chem. 2014;4:No. 99. doi: 10.1007/s40097-014-0099-9. DOI

Kolhatkar A, Jamison A, Litvinov D, Willson R, Lee T. Int J Mol Sci. 2013;14(8):15977–16009. doi: 10.3390/ijms140815977. PubMed DOI PMC

Patsula V, Moskvin M, Dutz S, Horák D. J Phys Chem Solids. 2016;88:24–30. doi: 10.1016/j.jpcs.2015.09.008. DOI

Silva M E, Dietrich C P. J Biol Chem. 1975;250:6841–6846. PubMed

Alquwaizani M, Buckley L, Adams C, Fanikos J. Curr Emerg Hosp Med Rep. 2013;1:83–97. doi: 10.1007/s40138-013-0014-6. PubMed DOI PMC

Pankhurst Q A, Connolly J, Jones S K, Dobson J. J Phys D: Appl Phys. 2003;36:R167–R181. doi: 10.1088/0022-3727/36/13/201. DOI

Bendary E, Francis R R, Ali H M G, Sarwat M I, El Hady S. Ann Agric Sci. 2013;58:173–181. doi: 10.1016/j.aoas.2013.07.002. DOI

Yang X, Du H, Liu J, Zhai G. Biomacromolecules. 2015;16:423–436. doi: 10.1021/bm501532e. PubMed DOI

Liang Y, Kiick K L. Acta Biomater. 2014;10:1588–1600. doi: 10.1016/j.actbio.2013.07.031. PubMed DOI PMC

Chen K, Xu X, Guo J, Zhang X, Han S, Wang R, Li X, Zhang J. Biomacromolecules. 2015;16:3574–3583. doi: 10.1021/acs.biomac.5b01056. PubMed DOI

Siow W X, Chang Y-T, Babič M, Lu Y-C, Horák D, Ma Y-H. Int J Nanomed. 2018;13:1693–1706. doi: 10.2147/ijn.s156029. PubMed DOI PMC

Shanehsazzadeh S, Lahooti A, Hajipour M J, Ghavami M, Azhdarzadeh M. Colloids Surf, B. 2015;136:1107–1112. doi: 10.1016/j.colsurfb.2015.11.028. PubMed DOI

Cheng Z, Ren J, Li Y, Chang W, Chen Z. Redox Rep. 2002;7:395–402. doi: 10.1179/135100002125001171. PubMed DOI

Curcio M, Puoci F, Iemma F, Parisi O I, Cirillo G, Spizzirri U G, Picci N. J Agric Food Chem. 2009;57:5933–5938. doi: 10.1021/jf900778u. PubMed DOI

Moskvin M, Babič M, Reis S, Cruz M M, Ferreira L P, Carvalho M D, Lima S A C, Horák D. Colloids Surf, B. 2018;161:35–41. doi: 10.1016/j.colsurfb.2017.10.034. PubMed DOI

Babic M, Horák D, Trchová M, Jendelová P, Glogarová K, Lesný P, Herynek V, Hájek M, Syková E. Bioconjugate Chem. 2008;19(3):740–750. doi: 10.1021/bc700410z. PubMed DOI

Lu Y-C, Chang F-Y, Tu S-J, Chen J-P, Ma Y-H. J Magn Magn Mater. 2017;427:71–80. doi: 10.1016/j.jmmm.2016.11.010. DOI

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