Activatable MR Prodrug for Targeted Delivery and Treatment of Cancer

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Spring 2021


In this study, a new multimodal theranostic tool is reported utilizing nanoceria delivery system conjugated with the ICAM1 antibody and a magnetic resonance (MR) probe as a prodrug with both MR and cytotoxic properties. The prodrug was synthesized from doxorubicin and phenyl-amine modified DTPA chelated with gadolinium utilizing dithiobis(succinimidyl propionate) (DSP) as a crosslinker. Nanoceria was synthesized from cerium oxide and polyacrylic acid using a water-based alkali precipitation technique. Doxorubicin and the synthesized prodrug were encapsulated separately within the nanoceria polymer matrix using a solvent diffusion method. The drug/prodrug-encapsulated nanoceria’s carboxylated surface was functionalized with the ICAM1 antibody utilizing EDC/NHS chemistries and the resulting formulations were purified and characterized by DLS, zeta potential, UV/Vis, and MR. The efficacy of this platform was measured by treating MDA-MB-231 breast cancer (TNBC) cells and MCF-7 cells with the drug/prodrug-loaded, ICAM1-conjugated nanoceria and analyzing the results of the treatment. Results were evaluated by cytotoxicity assays (MTT), fluorescence microscopy, reactive oxygen species determination, and comet assays. In all, the results show the nanoceria platform is target-specific to TNBC, and the encapsulated prodrug is able to be activated releasing doxorubicin and initiating apoptosis in an in vivo breast cancer model.


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