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

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 (APT_HER2) phage clone. Chemically synthesized APT_HER2 showed high affinity for its target protein (K_d ≈ 89 nM) and specifically bound HER2-overexpressing cells (NIH3T6.7) and tumor tissue slices. Next, we prepared HER2-specific-aptide-conjugated magneto-nanoclusters (APT_HER2-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 APT_HER2-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, APT_HER2-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 APT_HER2-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 APT_HER2-MNCs show promise as an efficient nanotheranostic system that enables specific cancer imaging as well as targeted therapy.