Design, preparation, andin vitrocharacterization of a trimodally-targeted nanomagnetic onco-theranostic system for cancer diagnosis and therapy

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Graphical abstractIn this study, the aim was to introduce and characterize a new trimodally-targeted nanomagnetic onco-theranostic system for simultaneous early diagnosis and efficient treatment of cancer. The onco-theranostic system was designed as it could target the tumor site through three targeting approach, i.e. magnetic, folic acid receptor, and pH sensitivity, and concurrently, due to the presence of superparamagnetic iron oxide nanoparticles (SPIONs) with super paramagnetic characteristics could be useful as MRI contrast agent for early cancer diagnosis. To achieve this goal, SPIONs were coated with chitosan and folic acid-conjugated chitosan via ionic gelation method in order to obtain non-targeted nanomagnetic onco-diagnostic (NT/NOD) and targeted nanomagnetic onco-diagnostic (T/NOD) systems. Finally, doxorubicin was loaded successfully into NT/NOD and T/NOD in order to obtain nanomagnetic onco-theranostic (NT/NOT) and targeted nanomagnetic onco-theranostic (T/NOT) systems. The entrapment efficiency and drug loading of T/NOT was determined to be 62.33 ± 5.20% and 10.26 ± 1.36%, respectively. MTT assay revealed that all systems were biocompatible within the concentration range investigated. Also, the T/NOT system showed the lowest IC50 comparing with free doxorubicin and NT/NOT system. In addition, uptake studies and competitive inhibition study verified the folate receptor mediated endocytosis of targeted system by MCF-7 as a folate receptor-positive cell line. The finding revealed that the extent of drug release from theranostic systems was pH-sensitive as it was higher at acidic media compared to that of in the neutral condition. Finally, T2-weighted phantom images, with an acceptable and dose-dependent resolution, proved the potential of T/NOT system as promising T2 MR contrast agent for diagnostic purpose. These finding proved that the prepared T/NOT system have great potential as a novel tumor-targeting nanotheranostic agent for simultaneous MRI imaging and treatment of folate receptor-positive cancers. Further studies are needed to test their behavior in vivo.

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