<b>Corrole Nanoparticles for Chemotherapy of Castration-Resistant Prostate Cancer and as Sonodynamic Agents for Pancreatic Cancer Treatment</b>

Abstract

A nanoparticle-based system, composed of the gallium(III) complex of a minimally substituted corrole that is coated by transferrin as a targeting vehicle (<b>3-Ga</b> NPs), has been used for pre-clinical evaluation of its efficacy against human metastatic castration-resistant prostate cancer (mCRPC) tumor xenografts. All mice (<i>N</i> = 9) responded to a dose of 10 mg/kg, with a remarkable tumor growth inhibition of 400% following 2 weeks of treatment; Ames and hERG tests excluded potential concerns regarding mutagenicity and cardiotoxicity, respectively. Also demonstrated is the potential application of these <b>3-Ga</b> NPs as sonodynamic agents for the preclinical treatment of pancreatic cancer. 10 mg/kg <b>3-Ga</b> NPs combined with exposure to ultrasound waves (2 min of 1 MHz 0.1 w/cm^<b>2</b> twice a week) induced up to 77% tumor shrinkage. Consistently, tumor/tissue distribution and serum levels of <b>3-Ga</b> NPs in mice revealed high tumor specificity, favorable pharmacokinetics, fast absorption, slower redistribution, and very slow drug clearance.