scholarly journals The Intrinsic Biological Identities of Iron Oxide Nanoparticles and Their Coatings: Unexplored Territory for Combinatorial Therapies

Nanomaterials ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 837 ◽  
Author(s):  
Vladimir Mulens-Arias ◽  
José Manuel Rojas ◽  
Domingo F. Barber

Over the last 20 years, iron oxide nanoparticles (IONPs) have been the subject of increasing investigation due to their potential use as theranostic agents. Their unique physical properties (physical identity), ample possibilities for surface modifications (synthetic identity), and the complex dynamics of their interaction with biological systems (biological identity) make IONPs a unique and fruitful resource for developing magnetic field-based therapeutic and diagnostic approaches to the treatment of diseases such as cancer. Like all nanomaterials, IONPs also interact with different cell types in vivo, a characteristic that ultimately determines their activity over the short and long term. Cells of the mononuclear phagocytic system (macrophages), dendritic cells (DCs), and endothelial cells (ECs) are engaged in the bulk of IONP encounters in the organism, and also determine IONP biodistribution. Therefore, the biological effects that IONPs trigger in these cells (biological identity) are of utmost importance to better understand and refine the efficacy of IONP-based theranostics. In the present review, which is focused on anti-cancer therapy, we discuss recent findings on the biological identities of IONPs, particularly as concerns their interactions with myeloid, endothelial, and tumor cells. Furthermore, we thoroughly discuss current understandings of the basic molecular mechanisms and complex interactions that govern IONP biological identity, and how these traits could be used as a stepping stone for future research.

2021 ◽  
Vol 12 ◽  
Author(s):  
Vladimir Mulens-Arias ◽  
José Manuel Rojas ◽  
Domingo F. Barber

The synthesis and functionalization of iron oxide nanoparticles (IONPs) is versatile, which has enhanced the interest in studying them as theranostic agents over recent years. As IONPs begin to be used for different biomedical applications, it is important to know how they affect the immune system and its different cell types, especially their interaction with the macrophages that are involved in their clearance. How immune cells respond to therapeutic interventions can condition the systemic and local tissue response, and hence, the final therapeutic outcome. Thus, it is fundamental to understand the effects that IONPs have on the immune response, especially in cancer immunotherapy. The biological effects of IONPs may be the result of intrinsic features of their iron oxide core, inducing reactive oxygen species (ROS) and modulating intracellular redox and iron metabolism. Alternatively, their effects are driven by the nanoparticle coating, for example, through cell membrane receptor engagement. Indeed, exploiting these properties of IONPs could lead to the development of innovative therapies. In this review, after a presentation of the elements that make up the tumor immunological microenvironment, we will review and discuss what is currently known about the immunomodulatory mechanisms triggered by IONPs, mainly focusing on macrophage polarization and reprogramming. Consequently, we will discuss the implications of these findings in the context of plausible therapeutic scenarios for cancer immunotherapy.


2019 ◽  
Vol 5 (10) ◽  
pp. FSO423
Author(s):  
Manuela Giraldo-Villegas ◽  
Jeaneth Urquijo ◽  
Oscar L Arnache-Olmos ◽  
Mauricio Rojas-López

Aim: To establish the effect of poly(acrylic acid)-coated iron oxide nanoparticles (PAC-IONs) and later exposure to a magnetic field on the differentiation of mononuclear phagocytes into macrophages. Methods: By flow cytometry, cell death was evaluated with DIOC6 and PI, Poly (ADP-ribose) Polymerases (PARP) fragmentation, H2AX phosphorylation and TUNEL assay. Cytokines by Cytokine bead array and the intracellular amount of iron by atomic absorption spectrometry. Results: PAC-IONs did not induce apoptosis, modify the cell membrane integrity or alter the mitochondrial membrane potential. They did not affect the cell morphology, the pattern of cytokine accumulation or the activating role of differentiation of mononuclear phagocytes into macrophages on the proliferation of autologous T cells. Conclusion: This evidence indicates that the PAC-IONs are safe and biocompatible. Moreover, the selectivity of the PAC-IONs for mononuclear phagocytes, as well as their increased uptake by non-classical monocytes, warrant future research with a view to their use as a contrast agent, a useful tool for in vivo tracking of tissue-infiltrating mononuclear phagocytes.


Nanomaterials ◽  
2018 ◽  
Vol 8 (8) ◽  
pp. 567 ◽  
Author(s):  
Hugo Groult ◽  
Isabel García-Álvarez ◽  
Lorenzo Romero-Ramírez ◽  
Manuel Nieto-Sampedro ◽  
Fernando Herranz ◽  
...  

The synthesis procedure of nanoparticles based on thermal degradation produces organic solvent dispersible iron oxide nanoparticles (OA-IONP) with oleic acid coating and unique physicochemical properties of the core. Some glycosides with hydrophilic sugar moieties bound to oleyl hydrophobic chains have antimitotic activity on cancer cells but reduced in vivo applications because of the intrinsic low solubility in physiological media, and are prone to enzymatic hydrolysis. In this manuscript, we have synthetized and characterized OA-IONP-based micelles encapsulated within amphiphilic bioactive glycosides. The glycoside-coated IONP micelles were tested as Magnetic Resonance Imaging (MRI) contrast agents as well as antimitotics on rat glioma (C6) and human lung carcinoma (A549) cell lines. Micelle antimitotic activity was compared with the activity of the corresponding free glycosides. In general, all OA-IONP-based micellar formulations of these glycosides maintained their anti-tumor effects, and, in one case, showed an unusual therapeutic improvement. Finally, the micelles presented optimal relaxometric properties for their use as T2-weighed MRI contrast agents. Our results suggest that these bioactive hydrophilic nano-formulations are theranostic agents with synergistic properties obtained from two entities, which separately are not ready for in vivo applications, and strengthen the possibility of using biomolecules as both a coating for OA-IONP micellar stabilization and as drugs for therapy.


2020 ◽  
Vol 20 (12) ◽  
pp. 942-945 ◽  
Author(s):  
Sekhar Talluri ◽  
Rama R. Malla

Background: The potential of Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) as theranostic agents for cancer has been investigated extensively. SPIONS can be utilized for diagnostic imaging, drug delivery as well as for therapeutic applications. SPIONS are of particular interest because of their potential for non-invasive diagnosis and non-invasive therapeutic applications. This article is a review of in vivo and clinical studies of SPIONs for diagnosis and treatment of breast, ovarian and cervical cancer. The current limitations of this technology with relation to clinical therapeutic applications and the potential to overcome these limitations are also discussed. Methods: NCBI Pubmed was searched for relevant documents by using keyword and MESH based search. The following keyword combinations were used: ‘breast cancer’ and SPION, ‘ovarian cancer’ and SPION, and ‘cervical cancer’ and SPION. The resulting list was manually scanned for the studies involving clinical and in vivo studies. Results: The 29 most relevant publications were identified and reviewed. Conclusion: Although numerous in vitro and in vivo studies have demonstrated the safety and effectiveness of the use of SPIONs for both diagnostic and therapeutic applications, there is relatively little progress towards translation to clinical applications involving breast, ovarian and cervical cancer.


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).


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 21 (12) ◽  
pp. 5812-5834
Author(s):  
Rachana Yadwade ◽  
Saili Kirtiwar ◽  
Balaprasad Ankamwar

Bio-fabrication of iron oxide nanoparticles by using different sources of plants, plant parts and microbial cells have become a great topic of interest nowadays due to its eco-friendly nature. The stabilizing and capping agents in biological sources are biocompatible, stable and non-toxic which make its use beneficial for various biomedical applications. The bacteria are able to utilize metal ions and convert them into their respective nanoparticles by secreting different biomolecules. The plants and plant parts contain different types of phytochemicals which play a key role in synthesis and bio-fabrication of nanoparticles. Iron oxide nanoparticles are known to have various applications in the fields of medicine, environment etc. This review summarizes the applications of iron oxide nanoparticles as antimicrobial agent, drug delivery agent, material for removal of heavy metals and dyes from aqueous system etc. Due to these wide applications of iron oxide nanoparticles its demand in various fields is increasing considerably. This review describes different approaches which are used for biosynthesis of iron oxide nanoparticles and their applications. The review also summarizes about the surface modification strategies of iron oxide nanoparticles by using different polymers, polyelectrolytes which can be used for in-vivo applications.


2016 ◽  
Vol 4 (3) ◽  
pp. 474-482 ◽  
Author(s):  
Ling Ding ◽  
Yong Hu ◽  
Yu Luo ◽  
Jianzhi Zhu ◽  
Yilun Wu ◽  
...  

LAPONITE®-stabilized iron oxide nanoparticles with great colloidal stability and high T2 relaxivity are synthesized by a facile controlled coprecipitation method, and can significantly enhance the contrast of tumors in vivo, indicating their tremendous potential in MR imaging applications.


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.


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