Biomaterial scaffolds for non-invasive focal hyperthermia as a potential tool to ablate metastatic cancer cells

Abstract

Currently, there are very few therapeutic options for treatment of metastatic disease, as it often remains undetected until the burden of disease is too high. Microporous poly(ε-caprolactone) biomaterials have been shown to attract metastasizing breast cancer cells in vivo early in tumor progression. In order to enhance the therapeutic potential of these scaffolds, they were modified such that infiltrating cells could be eliminated with non-invasive focal hyperthermia. Metal disks were incorporated into poly(ε-caprolactone) scaffolds to generate heat through electromagnetic induction by an oscillating magnetic field within a radiofrequency coil. Heat generation was modulated by varying the size of the metal disk, the strength of the magnetic field (at a fixed frequency), or the type of metal. When implanted subcutaneously in mice, the modified scaffolds were biocompatible and became properly integrated with the host tissue. Optimal parameters for in vivo heating were identified through a combination of computational modeling and ex vivo characterization to both predict and verify heat transfer dynamics and cell death kinetics during inductive heating. In vivo inductive heating of implanted, tissue-laden composite scaffolds led to tissue necrosis as seen by histological analysis. The ability to thermally ablate captured cells non-invasively using biomaterial scaffolds has the potential to extend the application of focal thermal therapies to disseminated cancers.

Iron oxide‐loaded polymer scaffolds for non‐invasive hyperthermic treatment of infiltrated cells

“…6 Previously, PCL-only scaffolds had been implanted into the subcutaneous space or wrapped in the gonadal fat pad within the intraperitoneal cavity, and 3-4 weeks of implantation was sufficient for cell infiltration. 11,16,33 Here, PCLonly scaffolds exhibited many nuclei and deposited extracellular matrix within pores after 3-4 weeks when attached to the intraperitoneal wall, but IO-loaded scaffolds required 6-7 weeks of implantation for similar levels of cell infiltration at this site. This decreased rate of infiltration is likely due to the low solubility of IO in water, thus making the IO-loaded scaffolds more hydrophobic, which will impact cell adhesion and consequently the rate of infiltration.…”

“…11,16 In our previous work, an aluminum disk was embedded in the center of these PCL scaffolds for hyperthermic treatment of infiltrated cells under an alternating magnetic field. 16 However, using a single thermal seed within the scaffold will provide less uniform heating versus a scaffold design containing a heat source that is distributed throughout, such as IO particles. Uniform scaffold heating allows for a lower maximum temperature needed within the scaffold for effective hyperthermia treatment of the entire scaffold, and a distributed heat source decreases the dependence of scaffold orientation (and its single thermal seed) with respect to the magnetic field on heating.…”

“…Once outside of the inductive coil, the magnetic field strength can vary during treatment, and it will decrease significantly at positions away from the center of the coil. 16,34 When the scaffold was placed within the alternating magnetic field, killing of infiltrated cells could be accomplished, as evidenced by the decrease in number of nuclei through H&E staining. The observation that some regions within a scaffold were treated successfully while others had many remaining cells displays the importance of properly positioning the IO-loaded scaffold within the magnetic field.…”

“…More recently, focal therapy methods have been coupled with biomaterial scaffolds which have previously been used to recruit metastatic cancer cells. Non‐invasive hyperthermia treatment of infiltrated cells was successfully completed in vivo using porous PCL scaffolds with an embedded aluminum disk under an alternating magnetic field 16 . Although heating of cells within the scaffold was achieved, the temperature gradient resulting from a single thermal seed at the center of the cylindrical scaffold requires longer treatment times to reach therapeutic temperatures at the radial edge of the scaffold and results in elevated temperatures in a significant region of surrounding tissue due to the scaffold geometry.…”

Genetically engineered magnetic nanocages for cancer magneto-catalytic theranostics

“…agnetic hyperthermia therapy (MHT) is a new approach for minimally invasive treatment of cancer 1,2 and has been tested in the clinic [3][4][5] . Among the various types of magnetic thermal induction agents, iron oxide nanoparticles (IONs) show some promise due to their safety and magnetic property (e.g., clinical contrast agents for magnetic resonance imaging (MRI)) [6][7][8] .…”