Controlling the transverse proton relaxivity of magnetic graphene oxide

Thapa, Bibek; Diaz-Diestra, Daysi; Badillo-Diaz, Dayra; Sharma, Rohit K.; Dasari, Kiran; Kumari, Shalini; Holcomb, Mikel B.; Beltran‐Huarac, Juan; Weiner, Brad R.; Morell, Gerardo

doi:10.1038/s41598-019-42093-1

Cited by 17 publications

(11 citation statements)

References 52 publications

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“…Hence, the shape of constituent nanoparticles in their ensemble framework with reduced symmetry of induced local field plays a critical role, because of magnetic field coupling between adjoining nanoparticles. Classical electrodynamic theory also explains that, except for ellipsoidal-shaped systems, all other distorting shapes require extra energy in order to stabilize the magnetic anisotropy. − Furthermore, the type of spin orientation, the distance between consecutive spins, and the relative motion of spins in such complex ensembles can influence proton–electron/proton–proton interaction, which further impacts on transverse relaxation. Hence, we require detailed exploration on the correlation between structure-regulated physical properties and transverse MRI contrast enhancement by considering differently organized ensembles of both isotropic and anisotropic nanosystems.…”

Section: Introductionmentioning

confidence: 99%

Structure-Correlated Magnetic Resonance Transverse Relaxivity Enhancement in Superparamagnetic Ensembles with Complex Anisotropy Landscape

et al. 2022

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The aim of the work is to explore structurerelaxivity relationship by observing transverse relaxivity enhancement in magnetic resonance imaging (MRI) of differently organized superparamagnetic complex ensembles of zinc ferrite isotropic/anisotropic nanosystems. We observe that superparamagnetic systems show a correlation of MRI-transverse relaxivity, r 2 /r 1 , with spatial arrangement of nanoparticles, as well as magnetic easy axes and thermal-energy-dependent anisotropy energy landscape. The presence of highly random/partially aligned easy axes with enhanced anisotropy constant leads to modulation in transverse relaxation. As a result, we achieve highest contrast efficiency in compact ensemble of isotropic nanoparticles and hollow core ensemble. Indeed, core−shell ensemble with combined effect of aligned and randomly oriented easy magnetic axes shows a reduction in MRI contrast efficiency. However, we address a hypothesis for transverse contrast efficiency where we depict the correlation among MRI-transverse contrast efficiency with structural complexity of ensembles, differently arranged primary nanoparticles/magnetic easy axes, anisotropy constant, and collective magnetic behavior. In consequence, we simplify the limitation of quantum mechanical outer-sphere diffusion model of magnetic resonance relaxivity by neglecting the contribution of magnetization and introducing an anisotropy constant contribution with complex structure landscape of easy axes.

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Section: Introductionmentioning

confidence: 99%

Structure-Correlated Magnetic Resonance Transverse Relaxivity Enhancement in Superparamagnetic Ensembles with Complex Anisotropy Landscape

et al. 2022

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“…Afterward, the solution was freeze-dried to obtain the final product. TEM images of cubic ND-PEG-SPIONs (0.100 mg/mL Fe) dispersed in water and cell culture media were recorded using a JEOL JEM 1230 transmission electron microscope, following a sample preparation procedure reported elsewhere. − The particle size, polydispersity index, and zeta potential of cubic ND-PEG-SPIONs (0.100 mg/mL Fe) were determined by using a DLS device (Malvern Zetasizer, Malvern Instruments). The magnetic response of cubic ND-PEG-SPIONs was measured by using a superconducting quantum interference device-vibrating sample magnetometer (SQUID-VSM, Quantum Design) at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Magnetic Control of Protein Expression via Magneto-mechanical Actuation of ND-PEGylated Iron Oxide Nanocubes for Cell Therapy

Beltran‐Huarac

Yamaleyeva

Dotti

et al. 2023

ACS Appl. Mater. Interfaces

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Engineered cells used as smart vehicles for delivery of secreted therapeutic proteins enable effective treatment of cancer and certain degenerative, autoimmune, and genetic disorders. However, current cell-based therapies use mostly invasive tools for tracking proteins and do not allow for controlled secretion of therapeutic proteins, which could result in unconstrained killing of surrounding healthy tissues or ineffective killing of host cancer cells. Regulating the expression of therapeutic proteins after success of therapy remains elusive. In this study, a noninvasive therapeutic approach mediated by magneto-mechanical actuation (MMA) was developed to remotely regulate the expression of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein, which is secreted by transduced cells. Stem cells, macrophages, and breast cancer cells were transduced with a lentiviral vector encoding the SGpL2TR protein. SGpL2TR comprises TRAIL and GpLuc domains optimized for cell-based applications. Our approach relies on the remote actuation of cubic-shape highly magnetic field responsive superparamagnetic iron oxide nanoparticles (SPIONs) coated with nitrodopamine PEG (ND-PEG), which are internalized within the cells. Cubic ND-PEG-SPIONs actuated by superlow frequency alternating current magnetic fields can translate magnetic forces into mechanical motion and in turn spur mechanosensitive cellular responses. Cubic ND-PEG-SPIONs were artificially designed to effectively operate at low magnetic field strengths (<100 mT) retaining approximately 60% of their saturation magnetization. Compared to other cells, stems cells were more sensitive to the interaction with actuated cubic ND-PEG-SPIONs, which clustered near the endoplasmic reticulum (ER). Luciferase, ELISA, and RT-qPCR analyses revealed a marked TRAIL downregulation (secretion levels were depleted down to 30%) when intracellular particles at 0.100 mg/mL Fe were actuated by magnetic fields (65 mT and 50 Hz for 30 min). Western blot studies indicated actuated, intracellular cubic ND-PEG-SPIONs can cause mild ER stress at short periods (up to 3 h) of postmagnetic field treatment thus leading to the unfolded protein response. We observed that the interaction of TRAIL polypeptides with ND-PEG can also contribute to this response. To prove the applicability of our approach, we used glioblastoma cells, which were exposed to TRAIL secreted from stem cells. We demonstrated that in the absence of MMA treatment, TRAIL essentially killed glioblastoma cells indiscriminately, but when treated with MMA, we were able to control the cell killing rate by adjusting the magnetic doses. This approach can expand the capabilities of stem cells to serve as smart vehicles for delivery of therapeutic proteins in a controlled manner without using interfering and expensive drugs, while retaining their potential to regenerate damaged tissue after treatment. This approach brings forth new alternatives to regulate protein expression noninvasively for cell therapy and other cancer therapies.

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“…More recently, safe-by-design magnetic NPs have been proposed as alternatives to circumvent limitations in NanoEL. In particular, superparamagnetic iron oxide NPs (SPIONs) have received FDA approval , and are being used as MRI contrast agents, − MPI tracers, agents to treat iron deficiency in anemia patients, and actuators in cancer therapy. − When a weak exogenous magnetic field is applied to SPIONs, the magnetic moment of the NPs becomes aligned in the direction of the field, which leads to a fast magnetic saturation. Turning the field off causes SPIONs to lose their magnetic properties, which averts the risk of reciprocal attraction and agglomeration .…”

Section: Introductionmentioning

confidence: 99%

Magneto-Mechanical Actuation Induces Endothelial Permeability

Kanber,

Umerah,

Brindley

et al. 2023

ACS Biomater. Sci. Eng.

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Cancer treatment is one of the major health problems that burden our society. According to the American Cancer Society, over 1.9 million new cancer cases and ∼0.6 million deaths from cancer are expected in the US in 2023. Therapeutic targeting is considered to be the gold standard in cancer treatment. However, when a tumor grows beyond a critical size, its vascular system differentiates abnormally and erratically, creating a heterogeneous endothelial barrier that further restricts drug delivery into tumors. While several methods exist, these prompt tumor migration and the appearance of new metastatic sites. Herein, we propose an innovative method based on magneto-mechanical actuation (MMA) to induce endothelial permeability. This method employs FDA-approved PEGylated superparamagnetic iron oxide nanoparticles (PEG-SPIONs) and alternating nonheating magnetic fields. MMA lies in the translation of magnetic forces into mechanical agitation. As a proof of concept, we developed a 2D cell culture model based on human umbilical vein endothelial cells (HUVEC), which were incubated with PEG-SPIONs and then exposed to different magnetic doses. After adjusting the particle concentration, incubation times, and parameters (amplitude, frequency, and exposure time) of the magnetic field generator, we induced actin filament remodeling and subsequent vascular endothelial-cadherin junction disruption. This led to transient gaps in cell monolayers, through which fluorescein isothiocyanate–dextran was translocated. We observed no cell viability reduction for 3 h of particle incubation up to a concentration of 100 μg/mL in the presence and absence of magnetic fields. For optimal permeability studies, the magnetic field parameters were adjusted to 100 mT, 65 Hz, and 30 min in a pulse mode with 5 min OFF intervals. We found that the endothelial permeability reached the highest value (33%) when 2 h postmagnetic field treatment was used. To explain these findings, a magneto-mechanical transduced stress mechanism mediated by intracellular forces was proposed. This method can open new avenues for targeted drug delivery into anatomic regions within the body for a broad range of disease interventions.

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Controlling the transverse proton relaxivity of magnetic graphene oxide

Cited by 17 publications

References 52 publications

Structure-Correlated Magnetic Resonance Transverse Relaxivity Enhancement in Superparamagnetic Ensembles with Complex Anisotropy Landscape

Structure-Correlated Magnetic Resonance Transverse Relaxivity Enhancement in Superparamagnetic Ensembles with Complex Anisotropy Landscape

Magnetic Control of Protein Expression via Magneto-mechanical Actuation of ND-PEGylated Iron Oxide Nanocubes for Cell Therapy

Magneto-Mechanical Actuation Induces Endothelial Permeability

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