Magnetic forces enable controlled drug delivery by disrupting endothelial cell-cell junctions

Qiu, Yongzhi; Tong, Sheng; Zhang, Linlin; Sakurai, Yumiko; Myers, David R.; Lin, Hong; Lam, Wilbur A.; Bao, Gang

doi:10.1038/ncomms15594

Cited by 147 publications

(128 citation statements)

References 51 publications

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“…Secondly, it was hypothesized that MNPSNPs are available in the implantation area. And thirdly, based on the results of previous in vitro and in vivo studies [26,53,54], an externally magnetized ferromagnetic implant material was supposed to be able to accumulate these nanoparticles at the implant surface in higher concentrations than the control. This would mean a safe use of MNPSNPs as future drug carrier system for implantassociated infection treatment.…”

Section: Discussionmentioning

confidence: 99%

“…This property was examined for a duration of up to 42 days. Secondly, it was hypothesized that the MNPSNPs were available in the implant area to a large extent due to PEG-surface with associated prolonged blood half-life, as well as enabled extravasation of MNPSNPs assuming comparably increased permeability as reported for similar but smaller nanoparticles in a study by Qiu et al [54]. Thirdly, based on our preliminary results, it was assumed that ferritic steel 1.4521 implants should attract significantly higher numbers of magnetic nanoparticles nanoparticles, this principle should enable reaching magnetizable implant surfaces at any time in any body region for a therapeutic reason.…”

Section: Introductionmentioning

confidence: 99%

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Biodistribution, biocompatibility and targeted accumulation of magnetic nanoporous silica nanoparticles as drug carrier in orthopedics

et al. 2020

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Background: In orthopedics, the treatment of implant-associated infections represents a high challenge. Especially, potent antibacterial effects at implant surfaces can only be achieved by the use of high doses of antibiotics, and still often fail. Drug-loaded magnetic nanoparticles are very promising for local selective therapy, enabling lower systemic antibiotic doses and reducing adverse side effects. The idea of the following study was the local accumulation of such nanoparticles by an externally applied magnetic field combined with a magnetizable implant. The examination of the biodistribution of the nanoparticles, their effective accumulation at the implant and possible adverse side effects were the focus. In a BALB/c mouse model (n = 50) ferritic steel 1.4521 and Ti90Al6V4 (control) implants were inserted subcutaneously at the hindlimbs. Afterwards, magnetic nanoporous silica nanoparticles (MNPSNPs), modified with rhodamine B isothiocyanate and polyethylene glycol-silane (PEG), were administered intravenously. Directly/1/7/21/42 day(s) after subsequent application of a magnetic field gradient produced by an electromagnet, the nanoparticle biodistribution was evaluated by smear samples, histology and multiphoton microscopy of organs. Additionally, a pathohistological examination was performed. Accumulation on and around implants was evaluated by droplet samples and histology.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Biodistribution, biocompatibility and targeted accumulation of magnetic nanoporous silica nanoparticles as drug carrier in orthopedics

et al. 2020

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“…The magnetic nanoparticles have been widely applied to in vivo use, such as magnetic resonance imaging (MRI) [1][2][3], magnetic-induced hyperthermia [4,5], switching cellular activity [6][7][8], or magnetically guided drug/gene delivery [9][10][11]. Among them, MRI is one of the key applications in which magnetic nanoparticles are used as contrast-enhancing agents for improving the sensitivity of MRI.…”

Section: Introductionmentioning

confidence: 99%

Precise Study on Size-Dependent Properties of Magnetic Iron Oxide Nanoparticles for In Vivo Magnetic Resonance Imaging

Chen

Xie

et al. 2018

Journal of Nanomaterials

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Developing a biocompatible contrast agent with high stability and favorable magnetism for sensitive detection of malignant tumors using magnetic resonance imaging (MRI) remains a great demand in clinical. Nowadays, the fine control of magnetic iron oxide nanoparticle (MION) sizes from a few nanometers to dozens of nanometers can be realized through a thermal decomposition method of iron precursors. This progress allows us to research accurately on the size dependence of magnetic properties of MION, involving saturation magnetization (M s ), specific absorption rate (SAR), and relaxivity. Here, we synthesized MION in a size range between 14 and 26 nm and modified them with DSPE-PEG2000 for biomedical use. The magnetic properties of PEGylated MION increased monotonically with MION size, while the nonspecific uptake of MION also enhanced with size through cell experiments. The MION with the size of 22 nm as a T2-weighted contrast agent presented the best contrastenhancing effect comparing with other sizes in vivo MRI of murine tumor. Therefore, the MION of 22 nm may have potential to serve as an ideal MRI contrast agent for tumor detection.

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“…In addition, we identified punctuate connexin43 (Cx43) immunosignal, suggesting the development of gap junctions ( Figure S6b, Supporting Information). [18] We could also identify cellular orientation in the area surrounding the high-density cells that could be attributed to the mechanical forces applied in the center of the construct due to the high number of CMs in this area (Figure 3a,b). This is consistent with previous studies showing that magnetic force can modulate F-actin dynamics and alignment.…”

Section: Doi: 101002/adma201904598mentioning

confidence: 99%

Remote Magnetic Nanoparticle Manipulation Enables the Dynamic Patterning of Cardiac Tissues

et al. 2019

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regenerative medicine and remains a major challenge. A multitude of technologies have been described to control the spatial organization of cells in 3D engineered heart constructs including mechanical strain/load [1] and chronic electrical stimulation. [2] Other approaches to guide cellular organization have been reported using microfluidic platforms, [3] light-triggered activation of biomolecules, [4] and 3D bioprinting. [5] However, these techniques often involve elaborate, macroscale stimulation systems and are not always suitable for the fabrication of detailed microarchitectures in vitro as each pattern requires new molds, posts, or frames. [6] The next generation of dynamic systems may be designed to respond to user-defined size and shape triggers for controlling cellular organization on the macroscale without the need for external mechanical supports or material cues. Magnetic procedures to manipulate and remotely control cellular behavior represent a promising approach for fabrication of tissuelike constructs. In particular, magnetic nanoparticles (MNPs) have gained increased attention for use in biomedical applications such as magnetic targeting of stem cells [7] and genes, [8] development of scaffold-free multilayer structures, [9] and spatial patterning of aggregates. [10] Magnetic techniques are advantageous due to their high precision and accuracy. To date, magnetic fabrication of biological structures has been illustrated by the assembly of biomembranes made of organized yeast, [11] the formation of "artificial retinas" by magnetic field modulation of chiromagnetic nanoparticles, [12] or the engineering of vocal folds, [13] among others.Here, we report a new platform for engineering tissue morphologies with controlled geometries. Specifically, we used magnetic fields to direct the assembly and patterning of magnetized human cardiomyocytes (CMs) labeled with MNPs in collagenbased hydrogels. Our system enables dynamic manipulation of cells within 3D biomaterials that can be applied to engineer patterned tissues to investigate cellular and tissue behavior. Furthermore, the simplicity and the faithful reproduction of our approach will enable the creation of customized 3D constructs with a new range of complementary implementations such as in biomedical devices, soft robotics, and flexible electronics.First, we designed functionalized MNPs to target and label human induced pluripotent-stem-cell-derived cardiomyocytes (hiPSC-CMs, Figure 1a). For that purpose, we conjugated an antisignal-regulatory protein alpha (SIRPA) cell surface mono clonal antibody [14] labeled with a fluorophore to three types of MNPsThe ability to manipulate cellular organization within soft materials has important potential in biomedicine and regenerative medicine; however, it often requires complex fabrication procedures. Here, a simple, cost-effective, and one-step approach that enables the control of cell orientation within 3D collagen hydrogels is developed to dynamically create various tailored microstructures of cardiac...

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Magnetic forces enable controlled drug delivery by disrupting endothelial cell-cell junctions

Cited by 147 publications

References 51 publications

Biodistribution, biocompatibility and targeted accumulation of magnetic nanoporous silica nanoparticles as drug carrier in orthopedics

Biodistribution, biocompatibility and targeted accumulation of magnetic nanoporous silica nanoparticles as drug carrier in orthopedics

Precise Study on Size-Dependent Properties of Magnetic Iron Oxide Nanoparticles for In Vivo Magnetic Resonance Imaging

Remote Magnetic Nanoparticle Manipulation Enables the Dynamic Patterning of Cardiac Tissues

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