Abstract 4459: Characterization of a novel magnetic nanoparticles formulation for cancer therapeutic applications

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA We have successfully engineered a magnetic nanoparticles (MAG-NPs) formulation using a multi-layer approach which can be used for drug/gene/biomolecule delivery, hyperthermia, and magnetic resonance imaging (MRI) applications in cancer therapeutics. Overcoming nanoparticles clearance by the immune system remains a major challenge. This formulation is designed to provide an additional surface layer as molecular “authentication” that the body does not recognize as foreign material. The interaction between the surface of nanoparticles and plasma proteins leads to nanoparticle-protein complex which determines the rational design of clinically useful formulations for cancer therapeutics. This formulation was very effective for inhibiting tumorigenic features in in vitro and in vivo cancer models. Therefore, we further studied our MAG-NPs formulation for biologically and clinically relevant characteristic features for its clinical translation. For this, we have examined the change in particle size, zeta potential, human serum protein adsorption, hemotoxicity, uptake, targeting cancer cells, and magnetic resonance imaging of the MAG-NPs formulation. No significant change was observed in particle size and zeta potential of nanoformulation with the incubation of 0.5 to 50 wt/wt% human serum. With increase of serum concentration and particle concentration there was a clear indication that apart from serum albumin and transferrin; apolipoprotein E (Apo-E, a surrogate marker for improved circulation of nanoparticles and enhanced crossing of the blood-brain barrier) also adsorbed on the surface of nanoparticles (determined by Western blot analysis). No significant primary or secondary structural alterations were observed in serum proteins through circular dichroism study. Hemolysis assay demonstrated almost no hemolysis at the tested concentrations (up to 1 mg/mL) for nanoparticles compared to the positive control (sodium dodecyl sulphate). Particle internalization and targeting cancer cells were observed in dose dependent manner and were not influenced by protein architecture on surface of nanoparticles. Additionally, this formulation has exhibited identical T1 relaxation times (∼1.1-1.6 s) and T2 relaxation times (∼ 13-14 ms) which suggests that our nanoparticles retained MRI properties even after serum proteins adsorption and drug/biomolecular encapsulation. Based on all these superior clinical characteristics, this MAG-NPs formulation can effectively be used for the delivery of drug/siRNA/miRNAs for cancer therapy, diagnosis, and imaging. Citation Format: Murali M. Yallapu, Neeraj Chauhan, Shadi F. Othman, Vahid Khalilzad-Sharghi, Meena Jaggi, Subhash C. Chauhan. Characterization of a novel magnetic nanoparticles formulation for cancer therapeutic applications. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4459. doi:10.1158/1538-7445.AM2014-4459