HER2-specific aptide conjugated magneto-nanoclusters for potential breast cancer imaging and therapy

J Mater Chem B. 2013 Sep 28;1(36):4576-4583. doi: 10.1039/c3tb20613k. Epub 2013 Jul 31.

Abstract

Here, we report a nanotheranostic system that enables simultaneous imaging and therapy of HER2-overexpressing tumors. We first screened an aptide-based phage library for HER2-specific peptide ligands, identifying a HER2-specific aptide (APTHER2) phage clone. Chemically synthesized APTHER2 showed high affinity for its target protein (Kd≈ 89 nM) and specifically bound HER2-overexpressing cells (NIH3T6.7) and tumor tissue slices. Next, we prepared HER2-specific-aptide-conjugated magneto-nanoclusters (APTHER2-MNCs) by a rehydration method using oleic acid-stabilized superparamagnetic iron oxide nanoparticles (SPIONs) and amphiphilic phospholipids, yielding nanoparticles with a hydrodynamic diameter of 47 ± 10 nm. The APTHER2-MNCs showed higher transverse (r2) relaxivity (∼180 mM-1 s-1) and greater drug-loading capacity compared to the equivalent isolated SPIONs (∼120 mM-1 s-1). When intravenously injected into HER2-overexpressing NIH3T6.7 tumor-bearing mice, APTHER2-MNCs substantially accumulated in tumor tissue, enhancing the relative signal by ∼45% at 3 h post-injection. This allowed us to detect the tumor using magnetic resonance imaging. Furthermore, after docetaxel loading, the drug-loaded APTHER2-MNCs remarkably inhibited the growth of HER2-overexpressing tumors (∼50% relative to controls) with little apparent toxicity, measured as changes in body weight. Together, these results indicate that APTHER2-MNCs show promise as an efficient nanotheranostic system that enables specific cancer imaging as well as targeted therapy.