scholarly journals Pharmacokinetics of Single Domain Antibodies and Conjugated Nanoparticles Using a Hybrid near Infrared Method

2021 ◽  
Vol 22 (16) ◽  
pp. 8695
Author(s):  
Shiran Su ◽  
Thomas J. Esparza ◽  
Duong Nguyen ◽  
Simone Mastrogiacomo ◽  
Joong H. Kim ◽  
...  

Iron oxide nanoparticles and single domain antibodies from camelids (VHHs) have been increasingly recognized for their potential uses for medical diagnosis and treatment. However, there have been relatively few detailed characterizations of their pharmacokinetics (PK). The aim of this study was to develop imaging methods and pharmacokinetic models to aid the future development of a novel family of brain MRI molecular contrast agents. An efficient near-infrared (NIR) imaging method was established to monitor VHH and VHH conjugated nanoparticle kinetics in mice using a hybrid approach: kinetics in blood were assessed by direct sampling, and kinetics in kidney, liver, and brain were assessed by serial in vivo NIR imaging. These studies were performed under “basal” circumstances in which the VHH constructs and VHH-conjugated nanoparticles do not substantially interact with targets nor cross the blood brain barrier. Using this approach, we constructed a five-compartment PK model that fits the data well for single VHHs, engineered VHH trimers, and iron oxide nanoparticles conjugated to VHH trimers. The establishment of the feasibility of these methods lays a foundation for future PK studies of candidate brain MRI molecular contrast agents.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Joong H. Kim ◽  
Stephen Dodd ◽  
Frank Q. Ye ◽  
Andrew K. Knutsen ◽  
Duong Nguyen ◽  
...  

AbstractMagnetic resonance imaging (MRI) is a widely used non-invasive methodology for both preclinical and clinical studies. However, MRI lacks molecular specificity. Molecular contrast agents for MRI would be highly beneficial for detecting specific pathological lesions and quantitatively evaluating therapeutic efficacy in vivo. In this study, an optimized Magnetization Prepared—RApid Gradient Echo (MP-RAGE) with 2 inversion times called MP2RAGE combined with advanced image co-registration is presented as an effective non-invasive methodology to quantitatively detect T1 MR contrast agents. The optimized MP2RAGE produced high quality in vivo mouse brain T1 (or R1 = 1/T1) map with high spatial resolution, 160 × 160 × 160 µm3 voxel at 9.4 T. Test–retest signal to noise was > 20 for most voxels. Extremely small iron oxide nanoparticles (ESIONPs) having 3 nm core size and 11 nm hydrodynamic radius after polyethylene glycol (PEG) coating were intracranially injected into mouse brain and detected as a proof-of-concept. Two independent MP2RAGE MR scans were performed pre- and post-injection of ESIONPs followed by advanced image co-registration. The comparison of two T1 (or R1) maps after image co-registration provided precise and quantitative assessment of the effects of the injected ESIONPs at each voxel. The proposed MR protocol has potential for future use in the detection of T1 molecular contrast agents.


Nanomaterials ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1950
Author(s):  
Rossella Canese ◽  
Federica Vurro ◽  
Pasquina Marzola

Starting from the mid-1990s, several iron oxide nanoparticles (NPs) were developed as MRI contrast agents. Since their sizes fall in the tenths of a nanometer range, after i.v. injection these NPs are preferentially captured by the reticuloendothelial system of the liver. They have therefore been proposed as liver-specific contrast agents. Even though their unfavorable cost/benefit ratio has led to their withdrawal from the market, innovative applications have recently prompted a renewal of interest in these NPs. One important and innovative application is as diagnostic agents in cancer immunotherapy, thanks to their ability to track tumor-associated macrophages (TAMs) in vivo. It is worth noting that iron oxide NPs may also have a therapeutic role, given their ability to alter macrophage polarization. This review is devoted to the most recent advances in applications of iron oxide NPs in tumor diagnosis and therapy. The intrinsic therapeutic effect of these NPs on tumor growth, their capability to alter macrophage polarization and their diagnostic potential are examined. Innovative strategies for NP-based drug delivery in tumors (e.g., magnetic resonance targeting) will also be described. Finally, the review looks at their role as tracers for innovative, and very promising, imaging techniques (magnetic particle imaging-MPI).


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Ahmad Abulfathi Umar ◽  
Muhamad Fazly Abdul Patah ◽  
Faisal Abnisa ◽  
Wan Mohd Ashri Wan Daud

AbstractMagnetic hyperthermia therapy (MHT) is a highly promising therapeutic modality for the treatment of different kinds of cancers and malignant tumors. The therapy is based on the concept that; iron oxide nanoparticles deposited at cancer sites can generate heat when exposed to an alternating current magnetic field or near infrared radiation and consequently destroying only the cancer cells by exploiting their vulnerability to heat. The fact that the treatment is at molecular level and that iron oxide nanoparticles provide more guided focus heating justifies its efficacy over treatment such as surgery, radiation therapy and chemotherapy. Nevertheless, the spread of MHT as the next-generation therapeutics has been shadowed by insufficient heating especially at the in vivo stage. This can be averted by modifying the iron oxide nanoparticle structure. To this end, various attempts have been made by developing a magnetic hybrid nanostructure capable of generating efficient heat. However, the synthesis method for each component (of the magnetic hybrid nanostructure) and the grafting process is now an issue. This has a direct effect on the performance of the magnetic hybrid nanostructure in MHT and other applications. The main objective of this review is to detail out the different materials, methods and characterization techniques that have been used so far in developing magnetic hybrid nanostructure. In view of this, we conducted a comprehensive review and present a road map for developing a magnetic hybrid nanostructure that is capable of generating optimum heat during MHT. We further summarize the various characterization techniques and necessary parameters to study in validating the efficiency of the magnetic hybrid nanostructure. Hopefully, this contribution will serve as a guide to researchers that are willing to evaluate the properties of their magnetic hybrid nanostructure.


Nanoscale ◽  
2019 ◽  
Vol 11 (27) ◽  
pp. 12905-12914 ◽  
Author(s):  
Manman Xie ◽  
Shijia Liu ◽  
Christopher J. Butch ◽  
Shaowei Liu ◽  
Ziyang Wang ◽  
...  

Superparamagnetic iron oxide nanoparticles (SPIONs) have a history of clinical use as contrast agents in T2 weighted MRI, though relatively low T2 relaxivity has caused them to fall out of favor as new faster MRI techniques have gained prominence.


2014 ◽  
Vol 16 (5) ◽  
Author(s):  
Jinquan Li ◽  
Zijian Zhou ◽  
Jianghua Feng ◽  
Shuhui Cai ◽  
Jinhao Gao ◽  
...  

MRS Advances ◽  
2020 ◽  
Vol 5 (42) ◽  
pp. 2157-2168
Author(s):  
Aileen O'Shea ◽  
Anushri Parakh ◽  
Rita Maria Lahoud ◽  
Sandeep Hedgire ◽  
Mukesh G Harisinghani

AbstractWhile the use of iron oxide nanoparticles as magnetic resonance contrast agents for clinical imaging is established, they are more recently experiencing renewed interest as alternatives to gadolinium-based contrast agents. Ultra-small iron oxide nanoparticles have unique pharmacokinetics, metabolic and imaging properties. These properties have led to improved techniques for imaging a variety of vascular, oncologic and inflammatory conditions with iron oxide nanoparticles. Current research efforts are aimed at harnessing the characteristics of these nanoparticles to advance magnetic resonance imaging techniques and explore new therapeutic potentials. While there are some limitations to the use of iron oxide nanoparticles, including allergies to parenteral iron and iron storage disorders, the practicable applications for these agents will continue to expand. The purpose of this review is to provide a brief overview of the history and synthesis of iron oxide nanoparticles, their current applications in clinical imaging and their prospective clinical applications.


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