Antitumor Activity of Auger Electron Emitter 111In Delivered by Modular Nanotransporter for Treatment of Bladder Cancer With EGFR Overexpression

Abstract

Gamma-ray emitting ¹¹¹In, which is extensively used for imaging, is also a source of short-range Auger electrons (AE). While exhibiting negligible effect outside cells, these AE become highly toxic near DNA within the cell nucleus. Therefore, these radionuclides can be used as a therapeutic anticancer agent if delivered precisely into the nuclei of tumor target cells. Modular nanotransporters (MNTs) designed to provide receptor-targeted delivery of short-range therapeutic cargoes into the nuclei of target cells are perspective candidates for specific intracellular delivery of AE emitters. The objective of this study was to evaluate the <i>in vitro</i> and <i>in vivo</i> efficacy of ¹¹¹In attached MNTs to kill human bladder cancer cells overexpressing epidermal growth factor receptor (EGFR). The cytotoxicity of ¹¹¹In delivered by the EGFR-targeted MNT (¹¹¹In-MNT) was greatly enhanced on EJ-, HT-1376-, and 5637-expressing EGFR bladder cancer cell lines compared with ¹¹¹In non-targeted control. <i>In vivo</i> microSPECT/CT imaging and antitumor efficacy studies revealed prolonged intratumoral retention of ¹¹¹In-MNT with <i>t</i>½ = 4.1 ± 0.5 days as well as significant dose-dependent tumor growth delay (up to 90% growth inhibition) after local infusion of ¹¹¹In-MNT in EJ xenograft-bearing mice.