Dynamic Magnetic Fields Remote-Control ApoptosisviaNanoparticle Rotation

Abstract

The ability to control the movement of nanoparticles remotely and with high precision would have far-reaching implications in many areas of nanotechnology. We have designed a unique dynamic magnetic field (DMF) generator that can induce rotational movements of superparamagnetic iron oxide nanoparticles (SPIONs). We examined whether the rotational nanoparticle movement could be used for remote induction of cell death by injuring lysosomal membrane structures. We further hypothesized that the shear forces created by the generation of oscillatory torques (incomplete rotation) of SPIONs bound to lysosomal membranes would cause membrane permeabilization, lead to extravasation of lysosomal contents into the cytoplasm, and induce apoptosis. To this end, we covalently conjugated SPIONs with antibodies targeting the lysosomal protein marker LAMP1 (LAMP1-SPION). Remote activation of slow rotation of LAMP1-SPIONs significantly improved the efficacy of cellular internalization of the nanoparticles. LAMP1-SPIONs then preferentially accumulated along the membrane in lysosomes in both rat insulinoma tumor cells and human pancreatic beta cells due to binding of LAMP1-SPIONs to endogenous LAMP1. Further activation of torques by the LAMP1-SPIONs bound to lysosomes resulted in rapid decrease in size and number of lysosomes, attributable to tearing of the lysosomal membrane by the shear force of the rotationally activated LAMP1-SPIONs. This remote activation resulted in an increased expression of early and late apoptotic markers and impaired cell growth. Our findings suggest that DMF treatment of lysosome-targeted nanoparticles offers a noninvasive tool to induce apoptosis remotely and could serve as an important platform technology for a wide range of biomedical applications.

“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

“…Nanocarriers combine chemotherapy with physically destructive modalities that induce tumor ablation (photothermal/magnetic) [218][219][220][221][222][223][224][225][226][227][228][229][230][231][232][233][234][235][236]245,246], generate reactive oxygen species (photodynamic) [232][233][234][235][236][237][238][239][240][241][242], and form of free radicals (radiotherapy) to maximize cancer eradication [243]. [246] and demonstrated higher anticancer activity in vitro and in vivo than PTX/PLGA/HAuNPs microspheres alone (no NIR-irradiation) or PLGA/HAuNPs microspheres (no PTX) with NIR irradiation. DOXloaded, PEG-conjugated hollow gold nanoparticles (DOX/PEG/ HAuNPs) demonstrated NIR-triggered, pH-dependent DOX release led to greater antitumor activity and decreased systemic toxicity than free DOX or liposomal DOX [218,219].…”

“…The pairing led to complete tumor eradication in vivo but the individual treatments only inhibited tumor growth, indicating the strong synergistic effect. In another approach, superparamagnetic iron oxide NPs (SPIONs) conjugated with lysosomal protein LAMP1-targeting antibodies induced apoptosis upon rotation activation by exposure to a magnetic field [246]. The NPs accumulated along the membrane in lysosomes due to the conjugated antibodies in rat insulinoma tumor cells and human pancreatic beta cells.…”

Mechanisms of Cellular Effects Directly Induced by Magnetic Nanoparticles under Magnetic Fields

“…Zhang et al demonstrated that isotropous Fe 3 O 4 nanoparticles could be rotationally activated in a unique dynamic magnetic field (20 Hz) and after MNPs were internalized into cells and bound to lysosomes, the rotationally activated MNPs generated shear forces which resulted in rapid decrease in size and number of lysosomes, attributable to tearing of the lysosomal membrane [41]. With regard to the effect induced by rotating MNPs under the magnetic field, Yue et al theoretically investigated the interaction mechanism between lipid membranes and rotating MNPs through simulation and found that the rotating nanoparticles promoted cell uptake and also induced the mechanical membrane rupture [89].…”

Electrochemical preparation and characterization of magnetic core–shell nanowires for biomedical applications

“…On the other hand, magnetic nanoparticles, especially of iron oxides, are being used in biomedicine for treatment as hyperthermia or drug delivery [6][7][8][9]. Recently, the possibility of using nickel nanowires in biomedicine has been also proposed [10][11][12].…”