Hyperthermia treatment of cancer cells by the application of targeted silk/iron oxide composite spheres.

ABSTRACT

Magnetic iron oxide nanoparticles (IONPs) are one of the most extensively studied materials for theranostic applications. IONPs can be used for magnetic resonance imaging (MRI), delivery of therapeutics, and hyperthermia treatment. Silk is a biocompatible material and can be used for biomedical applications. Previously, we produced spheres made of H2.1MS1 bioengineered silk that specifically carried a drug to the Her2-overexpressing cancer cells. To confer biocompatibility and targeting properties to IONPs, we blended these particles with bioengineered spider silks. Three bioengineered silks (MS1Fe1, MS1Fe2, and MS1Fe1Fe2) functionalized with the adhesion peptides F1 and F2, were constructed and investigated to form the composite spheres with IONPs carrying a positive or negative charge. Due to its highest IONP content, MS1Fe1 silk was used to produce spheres from the H2.1MS1MS1Fe silk blend to obtain a carrier with cell-targeting properties. Composite H2.1MS1MS1Fe1/IONP spheres made of silks blended at different ratios were obtained. Although the increased content of MS1Fe1 silk in particles resulted in an increased affinity of the spheres to IONPs, it decreased the binding of the composite particles to cancer cells. The H2.1MS1MS1Fe1 particles prepared at a ratio of 82 and loaded with IONPs exhibited the ability to bind to the targeted cancer cells similar to the control spheres without IONPs. Moreover, when exposed to the alternating magnetic field, these particles generated 2.5 times higher heat. They caused an almost three times higher percentage of apoptosis in cancer cells than the control particles. The blending of silks enabled the generation of cancer-targeting spheres with a high affinity for iron oxide nanoparticles, which can be used for anti-cancer hyperthermia therapy.