scholarly journals In Vivo Distribution of Poly(ethylene glycol) Functionalized Iron Oxide Nanoclusters: An Ultrastructural Study

Nanomaterials ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2184
Author(s):  
Maria Suciu ◽  
Claudiu Mirescu ◽  
Izabell Crăciunescu ◽  
Sergiu Gabriel Macavei ◽  
Cristian Leoștean ◽  
...  

The in vivo distribution of 50 nm clusters of polyethylene glycol-conjugated superparamagnetic iron oxide nanoparticles (SPIONs-PEG) was conducted in this study. SPIONs-PEG were synthesized de novo, and their structure and paramagnetic behaviors were analyzed by specific methods (TEM, DLS, XRD, VSM). Wistar rats were treated with 10 mg Fe/kg body weight SPIONs-PEG and their organs and blood were examined at two intervals for short-term (15, 30, 60, 180 min) and long-term (6, 12, 24 h) exposure evaluation. Most exposed organs were investigated through light and transmission electron microscopy, and blood and urine samples were examined through fluorescence spectrophotometry. SPIONs-PEG clusters entered the bloodstream after intraperitoneal and intravenous administrations and ended up in the urine, with the highest clearance at 12 h. The skin and spleen were within normal histological parameters, while the liver, kidney, brain, and lungs showed signs of transient local anoxia or other transient pathological affections. This study shows that once internalized, the synthesized SPIONs-PEG disperse well through the bloodstream with minor to nil induced tissue damage, are biocompatible, have good clearance, and are suited for biomedical applications.

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 179
Author(s):  
Alberto Curcio ◽  
Aurore Van de Walle ◽  
Christine Péchoux ◽  
Ali Abou-Hassan ◽  
Claire Wilhelm

Nanoparticles (NPs) are at the leading edge of nanomedicine, and determining their biosafety remains a mandatory precondition for biomedical applications. Herein, we explore the bioassimilation of copper sulfide NPs reported as powerful photo-responsive anticancer therapeutic agents. The nanoparticles investigated present a hollow shell morphology, that can be left empty (CuS NPs) or be filled with an iron oxide flower-like core (iron oxide@CuS NPs), and are compared with the iron oxide nanoparticles only (iron oxide NPs). CuS, iron oxide@CuS and iron oxide NPs were injected in 6-week-old mice, at doses coherent with an antitumoral treatment. Cu and Fe were quantified in the liver, spleen, kidneys, and lungs over 6 months, including the control animals, thus providing endogenous Cu and Fe levels in the first months after animal birth. After intravenous NPs administration, 77.0 ± 3.9% of the mass of Cu injected, and 78.6 ± 3.8% of the mass of Fe, were detected in the liver. In the spleen, we found 3.3 ± 0.6% of the injected Cu and 3.8 ± 0.6% for the Fe. No negative impact was observed on organ weight, nor on Cu or Fe homeostasis in the long term. The mass of the two metals returned to the control values within three months, a result that was confirmed by transmission electron microscopy and histology images. This bioassimilation with no negative impact comforts the possible translation of these nanomaterials into clinical practice.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1843
Author(s):  
Michał Żuk ◽  
Weronika Gawęda ◽  
Agnieszka Majkowska-Pilip ◽  
Magdalena Osial ◽  
Marcin Wolski ◽  
...  

Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used for biomedical applications for their outstanding properties such as facile functionalization and doping with different metals, high surface-to-volume ratio, superparamagnetism, and biocompatibility. This study was designed to synthesize and investigate multifunctional nanoparticle conjugate to act as both a magnetic agent, anticancer immunological drug, and radiopharmaceutic for anticancer therapy. The carrier, 166Ho doped iron oxide, was coated with an Au layer, creating core-shell nanoparticles ([166Ho] Fe3O4@Au. These nanoparticles were subsequently modified with monoclonal antibody trastuzumab (Tmab) to target HER2+ receptors. We describe the radiobioconjugate preparation involving doping of a radioactive agent and attachment of the organic linker and drug to the SPIONs’ surface. The size of the SPIONs coated with an Au shell measured by transmission electron microscopy was about 15 nm. The bioconjugation of trastuzumab onto SPIONs was confirmed by thermogravimetric analysis, and the amount of two molecules per one nanoparticle was estimated with the use of radioiodinated [131I]Tmab. The synthesized bioconjugates showed that they are efficient heat mediators and also exhibit a cytotoxic effect toward SKOV-3 ovarian cancer cells expressing HER2 receptors. Prepared radiobioconjugates reveal the high potential for in vivo application of the proposed multimodal hybrid system, combined with magnetic hyperthermia and immunotherapy against cancer tissues.


2017 ◽  
Vol 6 (5) ◽  
pp. 449-472 ◽  
Author(s):  
Marina Fontes de Paula Aguiar ◽  
Javier Bustamante Mamani ◽  
Taylla Klei Felix ◽  
Rafael Ferreira dos Reis ◽  
Helio Rodrigues da Silva ◽  
...  

AbstractThe purpose of this study was to review the use of the magnetic targeting technique, characterized by magnetic driving compounds based on superparamagnetic iron oxide nanoparticles (SPIONs), as drug delivery for a specific brain locus in gliomas. We reviewed a process mediated by the application of an external static magnetic field for targeting SPIONs in gliomas. A search of PubMed, Cochrane Library, Scopus, and Web of Science databases identified 228 studies, 23 of which were selected based on inclusion criteria and predetermined exclusion criteria. The articles were analyzed by physicochemical characteristics of SPIONs used, cell types used for tumor induction, characteristics of experimental glioma models, magnetic targeting technical parameters, and analysis method of process efficiency. The study shows the highlights and importance of magnetic targeting to optimize the magnetic targeting process as a therapeutic strategy for gliomas. Regardless of the intensity of the patterned magnetic field, the time of application of the field, and nanoparticle used (commercial or synthesized), all studies showed a vast advantage in the use of magnetic targeting, either alone or in combination with other techniques, for optimized glioma therapy. Therefore, this review elucidates the preclinical and therapeutic applications of magnetic targeting in glioma, an innovative nanobiotechnological method.


2021 ◽  
Vol 17 (2) ◽  
pp. 205-215
Author(s):  
Zhenbo Sun ◽  
Mingfang Luo ◽  
Jia Li ◽  
Ailing Wang ◽  
Xucheng Sun ◽  
...  

Imaging-guided cancer theranostic is a promising strategy for cancer diagnostic and therapeutic. Photodynamic therapy (PDT), as an approved treatment modality, is limited by the poor solubility and dispersion of photosensitizers (PS) in biological fluids. Herein, it is demonstrated that superparamagnetic iron oxide (SPIO)-based nanoparticles (SCFs), prepared by conjugated with Chlorin e6 (Ce6) and modified with folic acid (FA) on the surface, can be used as versatile drug delivery vehicles for effective PDT. The nanoparticles are great carriers for photosensitizer Ce6 with an extremely high loading efficiency. In vitro fluorescence imaging and in vivo magnetic resonance imaging (MRI) results indicated that SCFs selectively accumulated in tumor cells. Under near-infrared laser irradiation, SCFs were confirmed to be capable of inducing low cell viability of RM-1 cells In vitro and displaying efficient tumor ablation with negligible side effects in tumor-bearing mice models.


2010 ◽  
Vol 19 (4) ◽  
pp. 419-429 ◽  
Author(s):  
Po-Wah So ◽  
Tammy Kalber ◽  
David Hunt ◽  
Michael Farquharson ◽  
Alia Al-Ebraheem ◽  
...  

Determination of the dynamics of specific cell populations in vivo is essential for the development of cell-based therapies. For cell tracking by magnetic resonance imaging (MRI), cells need to internalize, or be surface labeled with a MRI contrast agent, such as superparamagnetic iron oxide nanoparticles (SPIOs): SPIOs give rise to signal loss by gradient-echo and T2-weighted MRI techniques. In this study, cancer cells were chemically tagged with biotin and then magnetically labeled with anti-biotin SPIOs. No significant detrimental effects on cell viability or death were observed following cell biotinylation. SPIO-labeled cells exhibited signal loss compared to non-SPIO-labeled cells by MRI in vitro. Consistent with the in vitro MRI data, signal attenuation was observed in vivo from SPIO-labeled cells injected into the muscle of the hind legs, or implanted subcutaneously into the flanks of mice, correlating with iron detection by histochemical and X-ray fluorescence (XRF) methods. To further validate this approach, human mesenchymal stem cells (hMSCs) were also employed. Chemical biotinylation and SPIO labeling of hMSCs were confirmed by fluorescence microscopy and flow cytometry. The procedure did not affect proliferation and multipotentiality, or lead to increased cell death. The SPIO-labeled hMSCs were shown to exhibit MRI signal reduction in vitro and was detectable in an in vivo model. In this study, we demonstrate a rapid, robust, and generic methodology that may be a useful and practical adjuvant to existing methods of cell labeling for in vivo monitoring by MRI. Further, we have shown the first application of XRF to provide iron maps to validate MRI data in SPIO-labeled cell tracking studies.


2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Zhan ◽  
Manish Muhuri ◽  
Phillip W. L. Tai ◽  
Guangping Gao

Conventional vaccinations and immunotherapies have encountered major roadblocks in preventing infectious diseases like HIV, influenza, and malaria. These challenges are due to the high genomic variation and immunomodulatory mechanisms inherent to these diseases. Passive transfer of broadly neutralizing antibodies may offer partial protection, but these treatments require repeated dosing. Some recombinant viral vectors, such as those based on lentiviruses and adeno-associated viruses (AAVs), can confer long-term transgene expression in the host after a single dose. Particularly, recombinant (r)AAVs have emerged as favorable vectors, given their high in vivo transduction efficiency, proven clinical efficacy, and low immunogenicity profiles. Hence, rAAVs are being explored to deliver recombinant antibodies to confer immunity against infections or to diminish the severity of disease. When used as a vaccination vector for the delivery of antigens, rAAVs enable de novo synthesis of foreign proteins with the conformation and topology that resemble those of natural pathogens. However, technical hurdles like pre-existing immunity to the rAAV capsid and production of anti-drug antibodies can reduce the efficacy of rAAV-vectored immunotherapies. This review summarizes rAAV-based prophylactic and therapeutic strategies developed against infectious diseases that are currently being tested in pre-clinical and clinical studies. Technical challenges and potential solutions will also be discussed.


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