Abstract
Lysosome-activated apoptosis represents an alternative method of overcoming tumor resistance compared to traditional forms of treatment. Pulsed magnetic fields open a new avenue for controlled and targeted initiation of lysosomal permeabilization in cancer cells via mechanical actuation of magnetic nanomaterials. In this study we used a noninvasive tool; namely, a benchtop pulsed magnetic system, which enabled remote activation of apoptosis in liver cancer cells. The magnetic system we designed represents a platform that can be used in a wide range of biomedical applications. We show that liver cancer cells can be loaded with superparamagnetic iron oxide nanoparticles (SPIONs). SPIONs retained in lysosomal compartments can be effectively actuated with a high intensity (up to 8 T), short pulse width (~15 µs), pulsed magnetic field (PMF), resulting in lysosomal membrane permeabilization (LMP) in cancer cells. We revealed that SPION-loaded lysosomes undergo LMP by assessing an increase in the cytosolic activity of the lysosomal cathepsin B. The extent of cell death induced by LMP correlated with the accumulation of reactive oxygen species in cells. LMP was achieved for estimated forces of 700 pN and higher. Furthermore, we validated our approach on a three-dimensional cellular culture model to be able to mimic in vivo conditions. Overall, our results show that PMF treatment of SPION-loaded lysosomes can be utilized as a noninvasive tool to remotely induce apoptosis.
Highlights
Iron oxide magnetic nanoparticles have been extensively utilized in a wide range of biomedical applications [1,2]
In this study we propose a fundamentally different approach of utilizing high intensity, short pulse width (~15 μs) pulsed magnetic field (PMF) produced by a compact, coolant-free system to induce apoptosis in a controlled manner via lysosomal membrane permeabilization (LMP) by transmitting mechanical force to clusters of superparamagnetic iron oxide nanoparticles (SPIONs) retained in lysosomes
Positive results from this study prompted us to explore the potential use of this system for remote actuation of cancer cell death via magneto-mechanical modulation of SPIONs
Summary
Iron oxide magnetic nanoparticles have been extensively utilized in a wide range of biomedical applications [1,2]. Unique physicochemical properties of superparamagnetic iron oxide nanoparticles (SPIONs) enable their use in diverse biomedical fields. Recent studies proposed the external application of magnetic fields as a simple, noninvasive tool to remotely control cell behavior via SPION mediated magneto-mechanical actuation [2,9]. Alternating magnetic fields have been successfully utilized for magneto-mechanical remote-control of SPIONs in a wide range of biomedical applications; e.g., magnetic tweezers, nanosensing, magnetic cell separation, specific delivery of genes and therapeutic agents, and mechanical modulation in cells [2,9,10,11]. Magnetic field-induced mechanical destruction of cells or cellular organelles was proposed as a promising potential tool for anti-cancer therapy [12,13,14,15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
