CMCTS stabilized Fe3O4 particles with extremely low toxicity as highly efficient near-infrared photothermal agents for in vivo tumor ablation

Abstract

With the potential uses of photothermal therapy (PTT) in cancer treatment with excellent efficacy, and the growing concerns about the nanotoxicity of hyperthermia agents such as carbon nanotubes and gold-based nanomaterials, the importance of searching for a biocompatible hyperthermia agent cannot be emphasized too much. In this work, a novel promising hyperthermia agent employing magnetic Fe₃O₄ particles with fairly low toxicity was proposed. This hyperthermia agent showed rapid heat generation under NIR irradiation. After modification with carboxymethyl chitosan (CMCTS), the obtained Fe₃O₄@CMCTS particles could disperse stably in PBS and serum without any aggregation. The modification of CMCTS could decrease the adsorption of bovine serum albumin (BSA) and improve the cellular uptake. In a comparative study with hollow gold nanospheres (HAuNS), Fe₃O₄@CMCTS particles exhibited a comparable photothermal effect and fairly low cytotoxicity. The in vivo magnetic resonance (MR) images of mice revealed that by attaching a magnet to the tumor, Fe₃O₄@CMCTS particles accumulated in the tumor after intravenous injection and showed a low distribution in the liver. After being exposed to a 808 nm laser for 5 min at a low power density of 1.5 W cm⁻², the tumors on Fe₃O₄@CMCTS-injected mice reached a temperature of ∼52 °C and were completely destroyed. Thus, a kind of multifunctional magnetic nanoparticle with extremely low toxicity and a simple structure for simultaneous MR imaging, targeted drug delivery and photothermal therapy can be easily fabricated.