T N T 2 0 1 8 � L e c c e ( I t a l y )

An In vivo Study On Cobalt Ferrite Nanoparticles As Multi-Modal Cancer Therapy Combining Intrinsic Toxicity and Hyperthermia

PreethiBalaBalakrishnan1,2FedericaMarinaro3,NiccoloSilvestri1,2,TizianoCatelani1,TeresaPellegrino11IstitutoItalianodiTecnologia,ViaMorego30,Genoa16162,Italy2UniversityofGenova,DCCI,ViaDodecaneso33,Genoa16146,Italy3GurdonInstitute,UniversityofCambridge,CambridgeCB21QN,UnitedKingdom

Preethi.balakrishnan@iit.itMagneticnanoparticlesunderalternatingmagneticfield can convert the electromagnetic energy intothermalenergywhich, inturncanbeexploitedforhyperthermia (HT) therapy1. Besides Iron Oxidenanoparticles(IONPs)whicharecommonlyusedasheathubsinmagnetichyperthermia,mixedferritesof these IONPswithManganese (Mn), Cobalt (Co)or Zinc (Zn) ions are alsopromising candidates forsuchmagneticHTtreatmentduetotheirimprovedmagneticproperties.Cobaltferritenanocubeshaveshown very high specific adsorption rate (SAR)values (a measure of their heat performances) atclinicallyacceptable frequencyandfieldconditions2. However, the use of Co-based nanoparticles forbiomedicalapplications isstillunderdebate.Thereare numerous evidences of intrinsic toxicity ofCoFe2O4 NPs in cellular studies, with a toxicityprofile being highly dependent on the cell typesand concentration tested3. Due to the provencytotoxicity, notmuch exploration has beenmadeoncobalt-basednanoparticlesinin-vivoconditions.We synthesized 17nm cobalt ferrite nanocubes bythermal decomposition method, which showedimproved SAR values at lower field and frequencyconditions compared to standard IONPs of similarsizeandshape2.Here,onaxenograftmurinemicemodel, we demonstrate the synergic effects ofcobaltferritenanocubesasmagnetichyperthermiainducing agents and intrinsic toxic agent withcontrolled Co ion release. The intra-tumoralinjection gave us the control, by specificallyinducing toxicity only at to tumor mass, avoidinguncontrolled toxicity to other vital organs. Theanimals treated with the combination of cobalt-ferrite injection and magnetic hyperthermiashowed complete reduction in tumor volume ascompared to untreated control and other groupsstudied (without HT, IONPswith andwithout HT).Furthermore, the same group showed the longestsurvival of up to 200 days post treatment. The

survived animals showed no signs of distressthroughout the study. Histopathological, TEM andelemental analysis were performed on tumor andorganssuchaskidney, liverandspleentostudy indetail the fateof thesenanoparticles invivo.Withtheresultsobtainedinourstudy,wedemonstratedthattheintrinsictoxicityoftheCoionsinthecobaltferrite nanocubes, when exploited in a controlledenvironment, can replace the usage of otherchemotherapeuticdrugsandact as a self-standingmulti-modal therapy, all working under lowerdosageandacceptablehyperthermialimits.References[1] KlausMaier-Hauff et al., Journal of Neuro-

Oncology,2007,81(1),pp53–60.[2] Ayyappan Sathya et al., Chem. Mater., 2016,

28(6),pp1769–1780.[3] Limor Horev-Azaria et al., Particle and Fibre

Toxicology2013,10:32.Figures

Figure 1. Schematic representation of preparation ofcobalt ferrite NPs for biomedical application (a) andtheir function as HT inducing agents (b). IR image ofanimal injected with Cobalt ferrite and subjected toHT(c).Imageofanimalbeforeandaftertreatment.