bioRxiv Science⌕ Search

bioRxiv · 10.1101/317115

Remote manipulation of magnetic nanoparticles using magnetic field gradient to promote cancer cell death

Abstract

The manipulation of magnetic nanoparticles (MNPs) using an external magnetic field, has been demonstrated to be useful in various biomedical applications. Some techniques have evolved utilizing this non-invasive external stimulus but the scientific community widely adopts few, and there is an excellent potential for more novel methods. The primary focus of this study is on understanding the manipulation of MNPs by a time-varying static magnetic field and how this can be used, at different frequencies and displacement, to manipulate cellular function. Here we explore, using numerical modeling, the physical mechanism which underlies this kind of manipulation, and we discuss potential improvements which would enhance such manipulation with its use in biomedical applications, i.e., increasing the MNP response by improving the field parameters. From our observations and other related studies, we infer that such manipulation depends mostly on the magnetic field gradient, the magnetic susceptibility and size of the MNPs, the magnet array oscillating frequency, the viscosity of the medium surrounding MNPs, and the distance between the magnetic field source and the MNPs. Additionally, we demonstrate cytotoxicity in neuroblastoma (SH-SY5Y) and hepatocellular carcinoma (HepG2) cells in vitro. This was induced by incubation with MNPs, followed by exposure to a magnetic field gradient, physically oscillating at various frequencies and displacement amplitudes. Even though this technique reliably produces MNP endocytosis and/or cytotoxicity, a better biophysical understanding is required to develop the mechanism used for this precision manipulation of MNPs, in vitro.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Subramanian, M., Miaskowski, A., Jenkins, S. I., Lim, J., Dobson, J.. 2018-05-22. Remote manipulation of magnetic nanoparticles using magnetic field gradient to promote cancer cell death. https://doi.org/10.1101/317115

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Engineering and characterisation of AAVS1 FRT cell lines for inducible and dose-dependent gene expression

Investigating biological function with high reproducibility requires the generation of stable cell lines that offer precise and inducible transgene expression. However, traditional methods often suffer from the limitations of random genomic integration, including unpredictable expression levels, leaky basal activity, and disruption of endogenous loci. To address these challenges, we engineered a versatile RPE1 cell line by integrating a TetOn3G-FRT cassette into the AAVS1 safe-harbour locus using CRISPR/Cas9(D10A) nickase. This platform utilises the Flp-FRT recombination system to facilitate rapid, site-specific "plug-and-play" insertion of transgenes, combined with the Tet-On 3G system for tight, dose-dependent expression control. The resulting RPE1 AAVS1 FRT8 line enables highly consistent transgene induction across independent clones, behaving as a monoclonal population. We highlight the importance of rigorous cell line characterisation through a multi-omics approach. Whole genome sequencing identified precise heterozygous integration at the target locus and de novo genomic duplications on other chromosomes. By integrating WGS with high-resolution proteomics and cell cycle analysis, we confirmed that these alterations did not significantly perturb cellular homeostasis or phenotypic fitness. This work establishes a robust and reliable platform for the efficient generation of inducible AAVS1 FRT stable cell lines, facilitating reproducible research in modern molecular biology.

bioengineering↗

Raman-probe-derived biomarkers account for cartilage composition, structure, and viscoelastic properties

Raman spectroscopy is an inelastic light scattering technique that reflects the vibrational modes of the biochemical building blocks of the major constituents that comprise the cartilage extracellular matrix (ECM): glycosaminoglycans (GAG), type-II collagen (COL), and water. We investigated whether ECM-specific biomarkers measured with our recently developed arthroscopy-compatible Raman needle probe characterize the functional viscoelastic properties of articular cartilage explants. Equine osteochondral explants were harvested from high-load (femoral condyle) and low-load (intertrochlear groove) sites to evaluate Raman-derived biomarkers of cartilage structure and function. Viscoelastic material properties (equilibrium/dynamic modulus, phase shift) were determined by mechanical indentation. A computational fibril-reinforced biphasic material model was used to estimate the glycosaminoglycan-associated non-fibrillar-matrix modulus, the collagen-associated fibril-network modulus, and hydraulic permeability. Raman-derived biomarkers enabled evaluation of cartilage tissue composition and structure, accounting for 81% of the variation in GAG content, 53% of the variation in COL content, and 58% of the variation in COL anisotropy. Biomarkers also accounted for 81% of the variation in equilibrium modulus, 58% in dynamic modulus, and 51% in phase shift. For poroelastic properties, biomarkers accounted for 83% of the variation in non-fibrillar-matrix modulus, 25% of the variation in fibril-network modulus, and 34% of the variation in hydraulic permeability. Clinical Significance: Raman spectroscopy provides objective compositional biomarkers that account for viscoelastic material properties underlying articular cartilage function. These findings support its future use as an arthroscopic platform for objective assessment of cartilage injury, monitoring of disease progression, and evaluation of therapeutic interventions.

bioengineering↗

An adjuvant for in vivo CAR-T therapy potentiation against solid tumors

In vivo CAR-T therapy offers rapid and controllable T-cell engineering but has yet to achieve durable efficacy against solid tumors. Rather than focusing solely on CAR-T cells, we harness the intact immune system via an in vivo CAR-T adjuvant (iCTA). Composed of aluminum-manganese hydrogel, iCTA can form a spatially confined antigenic and immunostimulatory niche in-situ. By coupling controlled antigen exposure with STING-type I interferon signaling, iCTA not only recruited and reactivated CAR-T cells, but engage the CAR-negative immunocytes with enhanced dendritic-cell antigen presentation and mobilized endogenous antigen-specific T-cell responses. Combined with mRNA-LNP-mediated in vivo CAR-T generation, a single administration of iCTA increased CAR+ T-cell abundance in draining lymph nodes and blood by 2-fold. It also increased T and NK cell infiltration, established an IFNgamma-enriched tumor microenvironment, and reduced exhaustion-associated T-cell states. iCTA improved tumor regression and survival, establishing an adjuvant strategy to enhance in vivo CAR-T therapy.

bioengineering↗