Pseudo single domain NiZn-γFe2O3 colloidal superparamagnetic nanoparticles for MRI-guided hyperthermia application

Nanotechnology ◽

10.1088/1361-6528/ac4353 ◽

2021 ◽

Author(s):

Ji-wook Kim ◽

JIE WANG ◽

Hyungsub Kim ◽

Seongtae Bae

Keyword(s):

Superparamagnetic Nanoparticles ◽

Single Domain ◽

Contrast Imaging ◽

Physical Reason ◽

Heat Induction ◽

Highly Efficient ◽

Magnetic Softness ◽

Mri Guided

Abstract MRI (Magnetic Resonance Imaging)-guided magnetic nanofluid hyperthermia (MNFH) is highly desirable in cancer treatment because it can allow for diagnosis, therapeutics, and prognosis simultaneously. However, the application of currently developed iron-oxide based superparamagnetic nanoparticles (IOSPNPs) for a MRI-guided MNFH agent is technically limited by the low AC heat induction power at the physiologically tolerable range of AC magnetic field (HAC,safe), and the low transverse r2-relaxivity responsible for the insufficient heating of cancers, and the low resolution of contrast imaging, respectively. Here, pseudo single domain colloidal NixZn1-x-γFe2O3 (x = 0.6) superparamagnetic nanoparticle (NiZn-γFe2O3 PSD-SPNP) physically and theoretically designed at the HAC,safe, specifically by the applied frequency, is proposed for a highly enhanced MRI-guided MNFH agent application. The NiZn-γFe2O3 PSD-SPNP showed the superparamagnetic characteristics, significantly enhanced AC heat induction performance, and highly improved saturation magnetization that are desirable for highly efficient MRI-guided MNFH agent applications. According to the analyzed results, the remarkably enhanced effective relaxation time constant and its dependent out-of-phase magnetic susceptibility as well as the DC/AC magnetic softness optimized by the PSD-SPNP at the HAC,safe were revealed as the main physical reason for the significance. All the fundamental in-vitro and in-vivo experimental results demonstrated that the physically designed NiZn-γFe2O3 PSD-SPNP is bio-technically feasible for a highly efficient MRI-guided MNFH agent for future cancer nanomedicine.

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Single Domain Antibodies as Carriers for Intracellular Drug Delivery: A Proof of Principle Study

Biomolecules ◽

10.3390/biom11070927 ◽

2021 ◽

Vol 11 (7) ◽

pp. 927

Author(s):

Sebas D. Pronk ◽

Erik Schooten ◽

Jurgen Heinen ◽

Esra Helfrich ◽

Sabrina Oliveira ◽

...

Keyword(s):

Drug Delivery ◽

Targeted Delivery ◽

Single Domain ◽

Drug Conjugates ◽

Intracellular Drug Delivery ◽

Internalization Rate ◽

Single Domain Antibodies ◽

Different Characteristics

Antibody-drug conjugates (ADCs) are currently used for the targeted delivery of drugs to diseased cells, but intracellular drug delivery and therefore efficacy may be suboptimal because of the large size, slow internalization and ineffective intracellular trafficking of the antibody. Using a phage display method selecting internalizing phages only, we developed internalizing single domain antibodies (sdAbs) with high binding affinity to rat PDGFRβ, a receptor involved in different types of diseases. We demonstrate that these constructs have different characteristics with respect to internalization rates but all traffic to lysosomes. To compare their efficacy in targeted drug delivery, we conjugated the sdAbs to a cytotoxic drug. The conjugates showed improved cytotoxicity correlating to their internalization speed. The efficacy of the conjugates was inhibited in the presence of vacuolin-1, an inhibitor of lysosomal maturation, suggesting lysosomal trafficking is needed for efficient drug release. In conclusion, sdAb constructs with different internalization rates can be designed against the same target, and sdAbs with a high internalization rate induce more cell killing than sdAbs with a lower internalization rate in vitro. Even though the overall efficacy should also be tested in vivo, sdAbs are particularly interesting formats to be explored to obtain different internalization rates.

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Highly efficient cell-mediated gene transfer using non-viral vectors and FuGene™6: in vitro and in vivo studies

Cellular and Molecular Life Sciences ◽

10.1007/pl00000769 ◽

2000 ◽

Vol 57 (8) ◽

pp. 1326-1333 ◽

Cited By ~ 30

Author(s):

I. Hellgren* ◽

V. Drvota ◽

R. Pieper ◽

S. Enoksson ◽

P. Blomberg ◽

...

Keyword(s):

Gene Transfer ◽

Viral Vectors ◽

In Vivo Studies ◽

Highly Efficient

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Distinct roles of tumor associated mutations in collective cell migration

Scientific Reports ◽

10.1038/s41598-021-89130-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Rachel M. Lee ◽

Michele I. Vitolo ◽

Wolfgang Losert ◽

Stuart S. Martin

Keyword(s):

Collective Behavior ◽

Metastatic Potential ◽

Breast Epithelial Cell ◽

Collective Cell Migration ◽

Label Free ◽

Collective Migration ◽

Contrast Imaging ◽

Pten Deletion

AbstractRecent evidence suggests that groups of cells are more likely to form clinically dangerous metastatic tumors, emphasizing the importance of understanding mechanisms underlying collective behavior. The emergent collective behavior of migrating cell sheets in vitro has been shown to be disrupted in tumorigenic cells but the connection between this behavior and in vivo tumorigenicity remains unclear. We use particle image velocimetry to measure a multidimensional migration phenotype for genetically defined human breast epithelial cell lines that range in their in vivo behavior from non-tumorigenic to aggressively metastatic. By using cells with controlled mutations, we show that PTEN deletion enhances collective migration, while Ras activation suppresses it, even when combined with PTEN deletion. These opposing effects on collective migration of two mutations that are frequently found in patient tumors could be exploited in the development of novel treatments for metastatic disease. Our methods are based on label-free phase contrast imaging, and thus could easily be applied to patient tumor cells. The short time scales of our approach do not require potentially selective growth, and thus in combination with label-free imaging would allow multidimensional collective migration phenotypes to be utilized in clinical assessments of metastatic potential.

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Novel cyclometalated iridium(iii) phosphine-imine (P^N) complexes: highly efficient anticancer and anti-lung metastasis agents in vivo

Inorganic Chemistry Frontiers ◽

10.1039/c9qi01492f ◽

2020 ◽

Vol 7 (5) ◽

pp. 1273-1283 ◽

Cited By ~ 2

Author(s):

Zhishan Xu ◽

Yuliang Yang ◽

Xianglei Jia ◽

Lihua Guo ◽

Xingxing Ge ◽

...

Keyword(s):

Lung Metastasis ◽

Tumour Growth ◽

Combined Treatment ◽

Highly Efficient

Iridium(iii)-based complexes with phosphine-imine (P^N) ligands are synthesized and authenticated. The combined treatment with Ir(iii) and BIX01294 potently inhibited tumour growth and lung metastasis in vitro and in vivo.

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A Pilot Study on Efficacy of Lipid Bubbles for Theranostics in Dogs with Tumors

Cancers ◽

10.3390/cancers12092423 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2423

Author(s):

Inoru Yokoe ◽

Yusuke Murahata ◽

Kazuki Harada ◽

Yuji Sunden ◽

Daiki Omata ◽

...

Keyword(s):

Cervical Region ◽

Focal Liver Lesions ◽

Contrast Imaging ◽

Contrast Enhanced Ultrasonography ◽

Series Of Experiments ◽

Diagnostic Applications ◽

Hepatic Portal ◽

Large Animals

The combined administration of microbubbles and ultrasound (US) is a promising strategy for theranostics, i.e., a combination of therapeutics and diagnostics. Lipid bubbles (LBs), which are experimental theranostic microbubbles, have demonstrated efficacy in vitro and in vivo for both contrast imaging and drug delivery in combination with US irradiation. To evaluate the clinical efficacy of LBs in combination with US in large animals, we performed a series of experiments, including clinical studies in dogs. First, contrast-enhanced ultrasonography using LBs (LB-CEUS) was performed on the livers of six healthy Beagles. The hepatic portal vein and liver tissue were enhanced; no adverse reactions were observed. Second, LB-CEUS was applied clinically to 21 dogs with focal liver lesions. The sensitivity and specificity were 100.0% and 83.3%, respectively. These results suggested that LB-CEUS could be used safely for diagnosis, with high accuracy. Finally, LBs were administered in combination with therapeutic US to three dogs with an anatomically unresectable solid tumor in the perianal and cervical region to determine the enhancement of the chemotherapeutic effect of liposomal doxorubicin; a notable reduction in tumor volume was observed. These findings indicate that LBs have potential for both therapeutic and diagnostic applications in dogs in combination with US irradiation.

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Ultrasmall superparamagnetic nanoparticles targeting E-selectin: synthesis and effects in mice in vitro and in vivo

International Journal of Nanomedicine ◽

10.2147/ijn.s199571 ◽

2019 ◽

Vol Volume 14 ◽

pp. 4517-4528 ◽

Cited By ~ 1

Author(s):

Lijuan Liu ◽

Lu Liu ◽

Yin Li ◽

Xiaoxin Huang ◽

Donglian Gu ◽

...

Keyword(s):

Superparamagnetic Nanoparticles

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1074-152 Will combinations of multiple agents produce more robust contrast imaging? An in vitro study and in vivo studies in dogs

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(04)91388-5 ◽

2004 ◽

Vol 43 (5) ◽

pp. A328

Author(s):

Xiaokui Li ◽

Hui Jiang ◽

Diane Paine ◽

Zuhua Mao ◽

Aarti Hejmadi Bhat ◽

...

Keyword(s):

In Vitro Study ◽

Vitro Study ◽

In Vivo Studies ◽

Multiple Agents ◽

Contrast Imaging

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Hyperthermia-Induced Controlled Local Anesthesia Administration Using Gelatin-Coated Iron–Gold Alloy Nanoparticles

Pharmaceutics ◽

10.3390/pharmaceutics12111097 ◽

2020 ◽

Vol 12 (11) ◽

pp. 1097

Author(s):

Chien-Kun Ting ◽

Udesh Dhawan ◽

Ching-Li Tseng ◽

Cihun-Siyong Alex Gong ◽

Wai-Ching Liu ◽

...

Keyword(s):

Local Anesthesia ◽

Gold Alloy ◽

Superparamagnetic Nanoparticles ◽

Alloy Nanoparticles ◽

Anesthetic Drug ◽

In Vivo Experiments ◽

In Vivo Cytotoxicity ◽

High Frequency Induction

The lack of optimal methods employing nanoparticles to administer local anesthesia often results in posing severe risks such as non-biocompatibility, in vivo cytotoxicity, and drug overdose to patients. Here, we employed magnetic field-induced hyperthermia to achieve localized anesthesia. We synthesized iron–gold alloy nanoparticles (FeAu Nps), conjugated an anesthetic drug, Lidocaine, and coated the product with gelatin to increase the biocompatibility, resulting in a FeAu@Gelatin–Lidocaine nano-complex formation. The biocompatibility of this drug–nanoparticle conjugate was evaluated in vitro, and its ability to trigger local anesthesia was also evaluated in vivo. Upon exposure to high-frequency induction waves (HFIW), 7.2 ± 2.8 nm sized superparamagnetic nanoparticles generated heat, which dissociated the gelatin coating, thereby triggering Lidocaine release. MTT assay revealed that 82% of cells were viable at 5 mg/mL concentration of Lidocaine, indicating that no significant cytotoxicity was induced. In vivo experiments revealed that unless stimulated with HFIW, Lidocaine was not released from the FeAu@Gelatin–Lidocaine complex. In a proof-of-concept experiment, an intramuscular injection of FeAu@Gelatin–Lidocaine complex was administered to the rat posterior leg, which upon HFIW stimulation triggered an anesthetic effect to the injected muscle. Based on our findings, the FeAu@Gelatin–Lidocaine complex can deliver hyperthermia-induced controlled anesthetic drug release and serve as an ideal candidate for site-specific anesthesia administration.

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Ni-Cu Nanoparticles and Their Feasibility for Magnetic Hyperthermia

Nanomaterials ◽

10.3390/nano10101988 ◽

2020 ◽

Vol 10 (10) ◽

pp. 1988 ◽

Cited By ~ 1

Author(s):

Bianca P. Meneses-Brassea ◽

Edgar A. Borrego ◽

Dawn S. Blazer ◽

Mohamed F. Sanad ◽

Shirin Pourmiri ◽

...

Keyword(s):

Magnetic Hyperthermia ◽

Biological Tissues ◽

Superparamagnetic Nanoparticles ◽

Blocking Temperature ◽

Ferromagnetic Behavior ◽

Cytotoxicity Test ◽

Cu Nanoparticles ◽

Hyperthermia Treatment

Ni-Cu nanoparticles have been synthesized by reducing Ni and Cu from metal precursors using a sol–gel route followed by annealing at 300 °C for 1, 2, 3, 6, 8, and 10 h for controlled self-regulating magnetic hyperthermia applications. Particle morphology and crystal structure revealed spherical nanoparticles with a cubic structure and an average size of 50, 60, 53, 87, and 87 nm for as-made and annealed samples at 300 °C for 1, 3, 6, and 10 h, respectively. Moreover, hysteresis loops indicated ferromagnetic behavior with saturation magnetization (Ms) ranging from 13–20 emu/g at 300 K. Additionally, Zero-filed cooled and field cooled (ZFC-FC) curves revealed that each sample contains superparamagnetic nanoparticles with a blocking temperature (TB) of 196–260 K. Their potential use for magnetic hyperthermia was tested under the therapeutic limits of an alternating magnetic field. The samples exhibited a heating rate ranging from 0.1 to 1.7 °C/min and a significant dissipated heating power measured as a specific absorption rate (SAR) of 6–80 W/g. The heating curves saturated after reaching the Curie temperature (Tc), ranging from 30–61 °C within the therapeutic temperature limit. An in vitro cytotoxicity test of these Ni-Cu samples in biological tissues was performed via exposing human breast cancer MDA-MB231 cells to a gradient of concentrations of the sample with 53 nm particles (annealed at 300 °C for 3 h) and reviewing their cytotoxic effects. For low concentrations, this sample showed no toxic effects to the cells, revealing its biocompatibility to be used in the future for in vitro/in vivo magnetic hyperthermia treatment of cancer.

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