Biodistribution, kinetics, and biological fate of SPION microbubbles in the rat

Barrefelt, Åsa; Saghafian, Maryam; Kuiper, Raoul V.; Ye, Fei; Egri, Gabriella; Klickermann, Moritz; Brismar, Torkel B.; Aspelin, Peter; Muhammed, Mamoun; Dähne, Lars; Hassan, Manal M.

doi:10.2147/ijn.s49948

Cited by 25 publications

(15 citation statements)

References 44 publications

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“…Indeed, we show that neutrophils and macrophages infiltrate subcutaneous tissue near the implants of CMC combined with NPs and internalize NPs released by CMC degradation. These data are in line with previous reports demonstrating the cytotoxicity of superparamagnetic iron oxide NPs in murine fibroblasts [13] and their accumulation in stromal cells, such as fibroblasts, and in macrophages, once injected in animals [26]. Although the inflammatory cells are involved in tumor progression and activation through production of pro-tumoral cytokines, control of tumour growth and dissemination by an active immune response cannot be excluded [27].…”

Section: Discussionsupporting

confidence: 91%

Monitoring Endothelial and Tissue Responses to Cobalt Ferrite Nanoparticles and Hybrid Hydrogels

et al. 2016

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Iron oxide nanoparticles (NPs) have been proposed for many biomedical applications as in vivo imaging and drug delivery in cancer treatment, but their toxicity is an ongoing concern. When NPs are intravenously administered, the endothelium represents the first barrier to tissue diffusion/penetration. However, there is little information about the biological effects of NPs on endothelial cells. In this work we showed that cobalt-ferrite (CoFe2O4) NPs affect endothelial cell integrity by increasing permeability, oxidative stress, inflammatory profile and by inducing cytoskeletal modifications. To overcome these problems, NPs have be loaded into biocompatible gels to form nanocomposite hybrid material (polysaccharide hydrogels containing magnetic NPs) that can be further conjugated with anticancer drugs to allow their release close to the target. The organic part of hybrid biomaterials is a carboxymethylcellulose (CMC) polymer, while the inorganic part consists of CoFe2O4 NPs coated with (3-aminopropyl)trimethoxysilane. The biological activity of these hybrid hydrogels was evaluated in vitro and in vivo. Our findings showed that hybrid hydrogels, instead of NPs alone, were not toxic on endothelial, stromal and epithelial cells, safe and biodegradable in vivo. In conclusion, biohydrogels with paramagnetic NPs as cross-linkers can be further exploited for antitumor drug loading and delivery systems.

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Section: Discussionsupporting

confidence: 91%

Monitoring Endothelial and Tissue Responses to Cobalt Ferrite Nanoparticles and Hybrid Hydrogels

et al. 2016

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“…Most of the MBs were found in the capillaries or phagocytosed by macrophages, preferably in the liver and spleen. 34 …”

Section: Resultsmentioning

confidence: 99%

Ultrasound contrast agent loaded with nitric oxide as a theranostic microdevice

Grishenkov¹,

Gonon²,

Weitzberg³

et al. 2015

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The current study describes novel multifunctional polymer-shelled microbubbles (MBs) loaded with nitric oxide (NO) for integrated therapeutic and diagnostic applications (ie, theranostics) of myocardial ischemia. We used gas-filled MBs with an average diameter of 4 μm stabilized by a biocompatible shell of polyvinyl alcohol. In vitro acoustic tests showed sufficient enhancement of the backscattered power (20 dB) acquired from the MBs’ suspension. The values of attenuation coefficient (0.8 dB/cm MHz) and phase velocities (1,517 m/s) were comparable with those reported for the soft tissue. Moreover, polymer MBs demonstrate increased stability compared with clinically approved contrast agents with a fracture threshold of about 900 kPa. In vitro chemiluminescence measurements demonstrated that dry powder of NO-loaded MBs releases its gas content in about 2 hours following an exponential decay profile with an exponential time constant equal to 36 minutes. The application of high-power ultrasound pulse (mechanical index =1.2) on the MBs resuspended in saline decreases the exponential time constant from 55 to 4 minutes in air-saturated solution and from 17 to 10 minutes in degassed solution. Thus, ultrasound-triggered release of NO is achieved. Cytotoxicity tests indicate that phagocytosis of the MBs by macrophages starts within 6–8 hours. This is a suitable time for initial diagnostics, treatment, and monitoring of the therapeutic effect using a single injection of the proposed multifunctional MBs.

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“…SPION-labeled dendritic cells showed potential for clinical use in assessing the therapeutic efficacy of dendritic cells by providing a visualization of their localization, thereby informing the relative effective dosage that was received and that the appropriate delivery site was accessed. Other studies have monitored the biodistribution and pharmacokinetic behavior of SPIONs in vivo using MRI as the NPs move throughout various organ systems 62–64 . This technique shows the non-invasive tracking capability of magnetite NPs as drugs move to the desired target.…”

Section: Spions In Cancer Diagnosis and Treatment Monitoringmentioning

confidence: 99%

Magnetite nanoparticles for cancer diagnosis, treatment, and treatment monitoring: recent advances

2016

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The development of nanoparticles (NPs) for use in all facets of oncological disease detection and therapy has shown great progress over the past two decades. NPs have been tailored for use as contrast enhancement agents for imaging, drug delivery vehicles, and most recently as a therapeutic component in initiating tumor cell death in magnetic and photonic ablation therapies. Of the many possible core constituents of NPs, such as gold, silver, carbon nanotubes, fullerenes, manganese oxide, lipids, micelles, etc., iron oxide (or magnetite) based NPs have been extensively investigated due to their excellent superparamagnetic, biocompatible, and biodegradable properties. This review addresses recent applications of magnetite NPs in diagnosis, treatment, and treatment monitoring of cancer. Finally, some views will be discussed concerning the toxicity and clinical translation of iron oxide NPs and the future outlook of NP development to facilitate multiple therapies in a single formulation for cancer theranostics.

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Biodistribution, kinetics, and biological fate of SPION microbubbles in the rat

Cited by 25 publications

References 44 publications

Monitoring Endothelial and Tissue Responses to Cobalt Ferrite Nanoparticles and Hybrid Hydrogels

Monitoring Endothelial and Tissue Responses to Cobalt Ferrite Nanoparticles and Hybrid Hydrogels

Ultrasound contrast agent loaded with nitric oxide as a theranostic microdevice

Magnetite nanoparticles for cancer diagnosis, treatment, and treatment monitoring: recent advances

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