Abstract 2875: Intravascular delivery of nanoclusters for treatment of prostate cancer with magnetic hyperthermia

Abstract

Abstract Prostate cancer is the leading cause of cancer death in American men. The high mortality rate is attributable to current treatments not providing a cure for hormone-refractory prostate cancer. The main goal of this project is to provide a novel therapeutic approach based on nanoparticle-mediated magnetic hyperthermia for efficient treatment of this cancer. Magnetic hyperthermia is a form of thermal therapy where magnetic nanoparticles delivered to cancer sites generate heat after exposure to an external alternating magnetic field (AMF). Many studies suggest that it has significant potential to kill cancer cells directly or enhance their susceptibility to radiation, chemotherapy and immunotherapy. Magnetic hyperthermia, however, is restricted to the treatment of localized and accessible tumors because therapeutic temperatures above 40 Celsius have only been achieved by intratumoral injection of magnetic nanoparticles. This is due to the low heating efficiency of conventional iron oxide nanoparticles combined with low tumor accumulation of these nanoparticles following systemic delivery. To employ this therapy for primary and metastatic prostate cancer tumors that are difficult to access for intratumoral injection, we have designed novel biocompatible nanoclusters with high heating efficiency that efficiently accumulate in prostate cancer tumors after intravenous injection at clinically relevant doses and generate the desirable intratumoral temperatures upon exposure to AMF. Our nanoclusters are built on hydrophobic iron oxide nanoparticles doped with zinc and manganese. To overcome challenges associated with poor water solubility of the synthesized nanoparticles, the solvent evaporation approach was employed to encapsulate and cluster them within the hydrophobic core of PEG-PCL-based polymeric nanoparticles. The amphiphilic PEG-PCL (methoxy poly(ethylene glycol)-b-poly(ϵ-caprolactone)) molecules, composed of hydrophobic 10 kDa PCL and hydrophilic 5 kDa PEG blocks, self-assemble in aqueous solution upon evaporation of the organic solvent to form nanoparticles with a hydrophilic PEG outer shell and hydrophobic PCL core. The transmission electron microscope images reveal that iron oxide nanoparticles form clusters within a single PEG-PCL nanoparticle. It is validated that the clustering of iron oxide nanoparticles enhances their heating efficiency. Animal studies demonstrate that following intravenous injection into mice bearing prostate cancer grafts the nanoclusters efficiently accumulate in cancer tumors and increase the intratumoral temperature up to 42 Celsius upon exposure to AMF. Finally, the systemically delivered magnetic hyperthermia significantly inhibits prostate cancer growth and does not exhibit any sign of toxicity. In summary, this discovery will allow to realize the true therapeutic potential of magnetic hyperthermia alone and in combination with other therapies for inaccessible primary and metastatic prostate cancer tumors. Citation Format: Oleh Taratula, Olena Taratula. Intravascular delivery of nanoclusters for treatment of prostate cancer with magnetic hyperthermia [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2875.