{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:05:22Z","timestamp":1760241922783,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2018,10,13]],"date-time":"2018-10-13T00:00:00Z","timestamp":1539388800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-006984","SFRH\/BD\/97658\/2013","RTChip4Theranostics"],"award-info":[{"award-number":["POCI-01-0145-FEDER-006984","SFRH\/BD\/97658\/2013","RTChip4Theranostics"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Slovene Research Agency","award":["J2-6754"],"award-info":[{"award-number":["J2-6754"]}]},{"name":"COST - European Cooperation in Science and Technology","award":["COST Action TD1402: RADIOMAG"],"award-info":[{"award-number":["COST Action TD1402: RADIOMAG"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["C"],"abstract":"<jats:p>A simple tailor-made protocol to synthesize graphene-based magnetic nanoparticles (GbMNPs) for nanomedicine is herein reported. Different GbMNPs with very distinctive physicochemical and toxicological properties were synthesized by adjusting the number of carbon precursors in the coating of superparamagnetic iron oxide nanoparticles. In vitro tests show the ability to use these GbMNPs as intelligent and on-demand drug nanocarrier systems for drug delivery, exhibiting the following features: good colloidal stability, good loading capacity of the chemotherapeutic drug doxorubicin, high pH-controlled release of the encapsulated drug (targeting tumour acidic pH conditions), superparamagnetic behaviour and biocompatibility. Due to their combined properties (i.e., physicochemical, magnetic, and biocompatibility), GbMNPs show high potentiality to be combined with other biomedical techniques, such as magnetic hyperthermia, which can represent an enhancement in the treatment of cancer.<\/jats:p>","DOI":"10.3390\/c4040055","type":"journal-article","created":{"date-parts":[[2018,10,15]],"date-time":"2018-10-15T03:43:01Z","timestamp":1539574981000},"page":"55","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Tailor-Made Protocol to Synthesize Yolk-Shell Graphene-Based Magnetic Nanoparticles for Nanomedicine"],"prefix":"10.3390","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4493-2654","authenticated-orcid":false,"given":"Raquel O.","family":"Rodrigues","sequence":"first","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o de Montanha (CIMO), Instituto Polit\u00e9cnico de Bragan\u00e7a, 5300-253 Bragan\u00e7a, Portugal"},{"name":"Laboratory of Separation and Reaction Engineering\u2014Laboratory of Catalysis and Materials (LSRE-LCM), Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"}]},{"given":"Giovanni","family":"Baldi","sequence":"additional","affiliation":[{"name":"CERICOL\u2014Centro Ricerche Colorobbia, Via Pietramarina 123, 50053 Sovigliana\u2014Vinci, Firenze, Italy"}]},{"given":"Saer","family":"Doumett","sequence":"additional","affiliation":[{"name":"CERICOL\u2014Centro Ricerche Colorobbia, Via Pietramarina 123, 50053 Sovigliana\u2014Vinci, Firenze, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2028-3234","authenticated-orcid":false,"given":"Juan","family":"Gallo","sequence":"additional","affiliation":[{"name":"Advanced (magnetic) Theranostic Nanostructures Lab, Life Sciences Department, INL\u2014International Iberian Nanotechnology Laboratory, Av. Mestre Jos\u00e9 Veiga, 4715-330 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4319-2631","authenticated-orcid":false,"given":"Manuel","family":"Ba\u00f1obre-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Advanced (magnetic) Theranostic Nanostructures Lab, Life Sciences Department, INL\u2014International Iberian Nanotechnology Laboratory, Av. Mestre Jos\u00e9 Veiga, 4715-330 Braga, Portugal"}]},{"given":"Goran","family":"Dra\u017ei\u0107","sequence":"additional","affiliation":[{"name":"Department for Materials Chemistry, National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana, Slovenia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6801-4578","authenticated-orcid":false,"given":"Ricardo C.","family":"Calhelha","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o de Montanha (CIMO), Instituto Polit\u00e9cnico de Bragan\u00e7a, 5300-253 Bragan\u00e7a, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4910-4882","authenticated-orcid":false,"given":"Isabel C. F. R.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o de Montanha (CIMO), Instituto Polit\u00e9cnico de Bragan\u00e7a, 5300-253 Bragan\u00e7a, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3428-637X","authenticated-orcid":false,"given":"Rui","family":"Lima","sequence":"additional","affiliation":[{"name":"MEtRICs\u2014Centro de Engenharia Mec\u00e2nica e Sustentabilidade de Recursos, Mechanical Engineering Department, University of Minho, Campus de Azur\u00e9m, 4800-058 Guimar\u00e3es, Portugal"},{"name":"CEFT\u2014Centro de Estudos de Fen\u00f3menos de Transporte, Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"}]},{"given":"Adri\u00e1n M. T.","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Separation and Reaction Engineering\u2014Laboratory of Catalysis and Materials (LSRE-LCM), Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6898-2408","authenticated-orcid":false,"given":"Helder T.","family":"Gomes","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o de Montanha (CIMO), Instituto Polit\u00e9cnico de Bragan\u00e7a, 5300-253 Bragan\u00e7a, Portugal"},{"name":"Laboratory of Separation and Reaction Engineering\u2014Laboratory of Catalysis and Materials (LSRE-LCM), Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2018,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4782","DOI":"10.1002\/smll.201601129","article-title":"Recent advances of using hybrid nanocarriers in remotely controlled therapeutic delivery","volume":"12","author":"Li","year":"2016","journal-title":"Small"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/nmat3776","article-title":"Stimuli-responsive nanocarriers for drug delivery","volume":"12","author":"Mura","year":"2013","journal-title":"Nat. Mater."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9050","DOI":"10.1021\/la701305f","article-title":"Fabrication of Magnetic Core@Shell Fe Oxide@Au Nanoparticles for Interfacial Bioactivity and Bio-separation","volume":"23","author":"Park","year":"2007","journal-title":"Langmuir"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2624","DOI":"10.1039\/c0nr00621a","article-title":"Synthesis of core-shell gold coated magnetic nanoparticles and their interaction with thiolated DNA","volume":"2","author":"Robinson","year":"2010","journal-title":"Nanoscale"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1007\/s40843-017-9022-1","article-title":"Synthesis of magnetic core-branched Au shell nanostructures and their application in cancer-related miRNA detection via SERS","volume":"60","author":"Yang","year":"2017","journal-title":"Sci. China Mater."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1021\/bm050820+","article-title":"Surface Modification of Silica Core-Shell Nanocapsules: Biomedical Implications","volume":"7","author":"Jovanovic","year":"2006","journal-title":"Biomacromolecules"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2964","DOI":"10.1166\/jnn.2012.6428","article-title":"Preparation and biomedical applications of core-shell silica\/magnetic nanoparticle composites","volume":"12","author":"Li","year":"2012","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"9437487","DOI":"10.1155\/2017\/9437487","article-title":"Superparamagnetic Iron Oxide (Fe3O4) Nanoparticles Coated with PEG\/PEI for Biomedical Applications: A Facile and Scalable Preparation Route Based on the Cathodic Electrochemical Deposition Method","volume":"2017","author":"Karimzadeh","year":"2017","journal-title":"Adv. Phys. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ijpharm.2010.10.011","article-title":"Stimuli-responsive magnetic particles for biomedical applications","volume":"403","author":"Medeiros","year":"2011","journal-title":"Int. J. Pharm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1007\/s11095-010-0260-1","article-title":"PEG-Functionalized Magnetic Nanoparticles for Drug Delivery and Magnetic Resonance Imaging Applications","volume":"27","author":"Yallapu","year":"2010","journal-title":"Pharm. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s13204-013-0216-y","article-title":"Magnetic nanoparticle drug delivery systems for targeting tumor","volume":"4","author":"Mody","year":"2014","journal-title":"Appl. Nanosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.bbrc.2015.08.022","article-title":"Magnetic nanoparticle-based drug delivery for cancer therapy","volume":"468","author":"Tietze","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.carbon.2016.01.094","article-title":"Gated mesoporous carbon nanoparticles as drug delivery system for stimuli-responsive controlled release","volume":"101","author":"Huang","year":"2016","journal-title":"Carbon"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1021\/acs.langmuir.5b03898","article-title":"Highly Hydrophilic Luminescent Magnetic Mesoporous Carbon Nanospheres for Controlled Release of Anticancer Drug and Multimodal Imaging","volume":"32","author":"Mohapatra","year":"2016","journal-title":"Langmuir"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1016\/j.drudis.2017.03.011","article-title":"Cancer-on-a-chip systems at the frontier of nanomedicine","volume":"22","author":"Zhang","year":"2017","journal-title":"Drug Discov. Today"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.2217\/nnm-2016-0133","article-title":"Boosting clinical translation of nanomedicine","volume":"11","author":"Jang","year":"2016","journal-title":"Nanomedicine"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"790","DOI":"10.3389\/fphar.2018.00790","article-title":"Current Trends and Challenges in the Clinical Translation of Nanoparticulate Nanomedicines: Pathways for Translational Development and Commercialization","volume":"9","author":"Hua","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"11718","DOI":"10.1039\/c3nr04032a","article-title":"Yolk-shell hybrid nanoparticles with magnetic and pH-sensitive properties for controlled anticancer drug delivery","volume":"5","author":"Li","year":"2013","journal-title":"Nanoscale"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"20543","DOI":"10.1038\/srep20543","article-title":"Multifunctional Nanocarpets for Cancer Theranostics: Remotely Controlled Graphene Nanoheaters for Thermo-Chemosensitisation and Magnetic Resonance Imaging","volume":"6","author":"Sasikala","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1021\/ja01539a017","article-title":"Preparation of Graphitic Oxide","volume":"80","author":"Hummers","year":"1958","journal-title":"J. Am. Chem. Soc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3157","DOI":"10.1021\/acs.iecr.5b04499","article-title":"Electrochemical Applications of Magnetic Core-Shell Graphene-Coated FeCo Nanoparticles","volume":"55","author":"Sarno","year":"2016","journal-title":"Ind. Eng. Chem. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11051-016-3498-7","article-title":"Haemocompatibility of iron oxide nanoparticles synthesized for theranostic applications: A high-sensitivity microfluidic tool","volume":"18","author":"Rodrigues","year":"2016","journal-title":"J. Nanopart. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.msec.2018.07.060","article-title":"Multifunctional graphene-based magnetic nanocarriers for combined hyperthermia and dual stimuli-responsive drug delivery","volume":"93","author":"Rodrigues","year":"2018","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9600","DOI":"10.1039\/C4TA01088D","article-title":"One-pot synthesis of yolk-shell mesoporous carbon spheres with high magnetisation","volume":"2","author":"Liu","year":"2014","journal-title":"J. Mater. Chem. A"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.apcatb.2016.06.021","article-title":"Magnetic carbon xerogels for the catalytic wet peroxide oxidation of sulfamethoxazole in environmentally relevant water matrices","volume":"199","author":"Ribeiro","year":"2016","journal-title":"Appl. Catal. B Environ."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5800","DOI":"10.1016\/j.ejmech.2011.09.029","article-title":"Anti-hepatocellular carcinoma activity using human HepG2 cells and hepatotoxicity of 6-substituted methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate derivatives: In vitro evaluation, cell cycle analysis and QSAR studies","volume":"46","author":"Abreu","year":"2011","journal-title":"Eur. J. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.indcrop.2016.10.046","article-title":"Bioactive properties and phenolic profile of Momordica charantia L. medicinal plant growing wild in Trinidad and Tobago","volume":"95","author":"Svobodova","year":"2017","journal-title":"Ind. Crops Prod."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"15529","DOI":"10.1039\/C5TA03179F","article-title":"Solvent-free mechanochemical synthesis of graphene oxide and Fe3O4-reduced graphene oxide nanocomposites for sensitive detection of nitrite","volume":"3","author":"Bharath","year":"2015","journal-title":"J. Mater. Chem. A"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7933","DOI":"10.1039\/c3ra46417b","article-title":"An in situ gelatin-assisted hydrothermal synthesis of ZnO-reduced graphene oxide composites with enhanced photocatalytic performance under ultraviolet and visible light","volume":"4","author":"Feng","year":"2014","journal-title":"RSC Adv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11829","DOI":"10.1038\/s41598-017-12200-1","article-title":"A generic method to synthesise graphitic carbon coated nanoparticles in large scale and their derivative polymer nanocomposites","volume":"7","author":"Wang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1186\/1556-276X-8-227","article-title":"A study of TiO2\/carbon black composition as counter electrode materials for dye-sensitized solar cells","volume":"8","author":"Lim","year":"2013","journal-title":"Nanoscale Res. Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.cattod.2016.04.040","article-title":"Hybrid magnetic graphitic nanocomposites for catalytic wet peroxide oxidation applications","volume":"280","author":"Ribeiro","year":"2017","journal-title":"Catal. Today"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"17944","DOI":"10.1039\/C8RA02017E","article-title":"Preparation of boron nitride nanosheet-coated carbon fibres and their enhanced antioxidant and microwave-absorbing properties","volume":"8","author":"Xu","year":"2018","journal-title":"RSC Adv."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"187401","DOI":"10.1103\/PhysRevLett.97.187401","article-title":"Raman Spectrum of Graphene and Graphene Layers","volume":"97","author":"Ferrari","year":"2006","journal-title":"Phys. Rev. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"14095","DOI":"10.1103\/PhysRevB.61.14095","article-title":"Interpretation of Raman spectra of disordered and amorphous carbon","volume":"61","author":"Ferrari","year":"2000","journal-title":"Phys. Rev. B"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.carbon.2013.08.038","article-title":"All in the graphene family\u2014A recommended nomenclature for two-dimensional carbon materials","volume":"65","author":"Bianco","year":"2013","journal-title":"Carbon"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"032183","DOI":"10.1063\/1.4756995","article-title":"A Raman spectroscopic investigation of graphite oxide derived graphene","volume":"2","author":"Kaniyoor","year":"2012","journal-title":"AIP Adv."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1021\/mp100269f","article-title":"Doxorubicin as a Molecular Nanotheranostic Agent: Effect of Doxorubicin Encapsulation in Micelles or Nanoemulsions on the Ultrasound-Mediated Intracellular Delivery and Nuclear Trafficking","volume":"7","author":"Mohan","year":"2010","journal-title":"Mol. Pharm."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"7441","DOI":"10.1039\/C6TB00746E","article-title":"Molecular simulation of pH-dependent diffusion, loading, and release of doxorubicin in graphene and graphene oxide drug delivery systems","volume":"4","author":"Mahdavi","year":"2016","journal-title":"J. Mater. Chem. B"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.ijpharm.2013.04.053","article-title":"Triggered pH\/redox responsive release of doxorubicin from prepared highly stable graphene with thiol grafted Pluronic","volume":"450","author":"Lee","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_41","first-page":"329","article-title":"Role of oxygen functionalities on the synthesis of photocatalytically active graphene-TiO2 composites","volume":"158\u2013159","author":"Likodimos","year":"2014","journal-title":"Appl. Catal. B Environ."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.dyepig.2007.03.001","article-title":"Effect of solution pH, ionic strength, and temperature on adsorption behavior of reactive dyes on activated carbon","volume":"77","author":"Walker","year":"2008","journal-title":"Dyes Pigments"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1021\/mp1002398","article-title":"Atomistic Simulation and Measurement of pH Dependent Cancer Therapeutic Interactions with Nanodiamond Carrier","volume":"8","author":"Adnan","year":"2011","journal-title":"Mol. Pharm."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.jconrel.2015.04.021","article-title":"Theranostic applications of carbon nanomaterials in cancer: Focus on imaging and cargo delivery","volume":"210","author":"Chen","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1021\/tx200339h","article-title":"Biological Interactions of Graphene-Family Nanomaterials\u2014An Interdisciplinary Review","volume":"25","author":"Sanchez","year":"2012","journal-title":"Chem. Res. Toxicol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.msec.2015.12.073","article-title":"Biomedical applications of the graphene-based materials","volume":"61","author":"Zhang","year":"2016","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2726","DOI":"10.1021\/acs.biomac.6b00786","article-title":"Naturally Derived Iron Oxide Nanowires from Bacteria for Magnetically Triggered Drug Release and Cancer Hyperthermia in 2D and 3D Culture Environments: Bacteria Biofilm to Potent Cancer Therapeutic","volume":"17","author":"Kumeria","year":"2016","journal-title":"Biomacromolecules"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s12274-012-0200-y","article-title":"A functionalized graphene oxide-iron oxide nanocomposite for magnetically targeted drug delivery, photothermal therapy, and magnetic resonance imaging","volume":"5","author":"Ma","year":"2012","journal-title":"Nano Res."}],"container-title":["C"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2311-5629\/4\/4\/55\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:25:30Z","timestamp":1760196330000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2311-5629\/4\/4\/55"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,13]]},"references-count":48,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["c4040055"],"URL":"https:\/\/doi.org\/10.3390\/c4040055","relation":{},"ISSN":["2311-5629"],"issn-type":[{"type":"electronic","value":"2311-5629"}],"subject":[],"published":{"date-parts":[[2018,10,13]]}}}