Morteza Mahmoudi

The adult mammalian heart possesses only limited capacity for innate regeneration and the response to severe injury is dominated by the formation of scar tissue. Current therapy to replace damaged cardiac tissue is limited to cardiac transplantation and thus many patients suffer progressive decay in the heart's pumping capacity to the point of heart failure. Nanostructured systems have the potential to revolutionize both preventive and therapeutic approaches for treating cardiovascular disease.… Show more

The adult mammalian heart possesses only limited capacity for innate regeneration and the response to severe injury is dominated by the formation of scar tissue. Current therapy to replace damaged cardiac tissue is limited to cardiac transplantation and thus many patients suffer progressive decay in the heart's pumping capacity to the point of heart failure. Nanostructured systems have the potential to revolutionize both preventive and therapeutic approaches for treating cardiovascular disease. Here, we outline recent advancements in nanotechnology that could be exploited to overcome the major obstacles in the prevention of and therapy for heart disease. We also discuss emerging trends in nanotechnology affecting the cardiovascular field that may offer new hope for patients suffering massive heart attacks. Show less

Platelets delivering the immunotherapeutic antibody anti-PD-L1 to the site of surgically removed tumours reduce cancer recurrence and metastatic spread in mice.

Until now, the Food and Drug Administration (FDA)-approved iron supplement ferumoxytol and other iron oxide nanoparticles have been used for treating iron deficiency, as contrast agents for magnetic resonance imaging and as drug carriers. Here, we show an intrinsic therapeutic effect of ferumoxytol on the growth of early mammary cancers, and lung cancer metastases in liver and lungs. In vitro, adenocarcinoma cells co-incubated with ferumoxytol and macrophages showed increased caspase-3… Show more

Until now, the Food and Drug Administration (FDA)-approved iron supplement ferumoxytol and other iron oxide nanoparticles have been used for treating iron deficiency, as contrast agents for magnetic resonance imaging and as drug carriers. Here, we show an intrinsic therapeutic effect of ferumoxytol on the growth of early mammary cancers, and lung cancer metastases in liver and lungs. In vitro, adenocarcinoma cells co-incubated with ferumoxytol and macrophages showed increased caspase-3 activity. Macrophages exposed to ferumoxytol displayed increased mRNA associated with pro-inflammatory Th1-type responses. In vivo, ferumoxytol significantly inhibited growth of subcutaneous adenocarcinomas in mice. In addition, intravenous ferumoxytol treatment before intravenous tumour cell challenge prevented development of liver metastasis. Fluorescence-activated cell sorting (FACS) and histopathology studies showed that the observed tumour growth inhibition was accompanied by increased presence of pro-inflammatory M1 macrophages in the tumour tissues. Our results suggest that ferumoxytol could be applied ‘off label’ to protect the liver from metastatic seeds and potentiate macrophage-modulating cancer immunotherapies. Show less

Using a family of cationic gold nanoparticles (NPs) with similar size and charge, we demonstrate that proper surface engineering can control the nature and identity of protein corona in physiological serum conditions. The protein coronas were highly dependent on the hydrophobicity and arrangement of chemical motifs on NP surface. The NPs were uptaken in macrophages in a corona-dependent manner, predominantly through recognition of specific complement proteins in the NP corona. Taken together… Show more

Using a family of cationic gold nanoparticles (NPs) with similar size and charge, we demonstrate that proper surface engineering can control the nature and identity of protein corona in physiological serum conditions. The protein coronas were highly dependent on the hydrophobicity and arrangement of chemical motifs on NP surface. The NPs were uptaken in macrophages in a corona-dependent manner, predominantly through recognition of specific complement proteins in the NP corona. Taken together, this study shows that surface functionality can be used to tune the protein corona formed on NP surface, dictating the interaction of NPs with macrophages. Show less

To control liposomes fate and transport upon contact with biofluids, it is essential to consider several parameters affecting the synthetic and biological identity of liposomes, as well as liposome–protein corona (PC) aspects. As a powerful tool in this data mining adventure, quantitative structure–activity relationship (QSAR) approach is used to correlate physicochemical properties of liposomes and their PC fingerprints to multiple quantified biological responses. In the present study, the… Show more

To control liposomes fate and transport upon contact with biofluids, it is essential to consider several parameters affecting the synthetic and biological identity of liposomes, as well as liposome–protein corona (PC) aspects. As a powerful tool in this data mining adventure, quantitative structure–activity relationship (QSAR) approach is used to correlate physicochemical properties of liposomes and their PC fingerprints to multiple quantified biological responses. In the present study, the relationship between cellular interactions of a set of structurally diverse liposomal formulations and their physicochemical and PC properties has been investigated via linear and nonlinear QSAR models. Significant parameters affecting cellular uptake and cell viability of liposomes in two important cancer cell lines (PC3 and HeLa) have been identified. The developed QSARs have the capacity to be implemented in advanced targeted delivery of liposomal drugs. Show less

Nanoparticles (NPs) are functionalized with targeting ligands to enable selectively delivering drugs to desired locations in the body. When these functionalized NPs enter the blood stream, plasma proteins bind to their surfaces, forming a protein corona that affects NP uptake and targeting efficiency. To address this problem, new strategies for directing the formation of a protein corona that has targeting capabilities are emerging. Here, we have investigated the feasibility of directing corona… Show more

Nanoparticles (NPs) are functionalized with targeting ligands to enable selectively delivering drugs to desired locations in the body. When these functionalized NPs enter the blood stream, plasma proteins bind to their surfaces, forming a protein corona that affects NP uptake and targeting efficiency. To address this problem, new strategies for directing the formation of a protein corona that has targeting capabilities are emerging. Here, we have investigated the feasibility of directing corona composition to promote targeted NP uptake by specific types of cells. We used the well-characterized process of opsonin-induced phagocytosis by macrophages as a simplified model of corona-mediated NP uptake by a desired cell type. We demonstrate that pre-coating silica NPs with gamma-globulins (γ-globulins) produced a protein corona that was enriched with opsonins, such as immunoglobulins. Although immunoglobulins are ligands that bind to receptors on macrophages and elicit phagocytois, the opsonin-rich protein corona did not increase NP uptake by macrophage RAW 264.7 cells. Immunolabeling experiments indicated that the binding of opsonins to their target cell surface receptors was impeded by other proteins in the corona. Thus, corona-mediated NP targeting strategies must optimize both the recruitment of the desired plasma proteins as well as their accessibility and orientation in the corona layer. Show less

A simple colorimetric sensor array technique was developed for the detection of various different nanoparticles (NPs) in aqueous solutions. The sensor array consists of five different cross-reactive chemoresponsive dyes, whose visible absorbances change in response to their interactions with NPs. Although no single dye is specific for any one NP, the pattern of color changes for all dyes provides a unique molecular fingerprint for each type of NP studied. Based on the responses of various dyes,… Show more

A simple colorimetric sensor array technique was developed for the detection of various different nanoparticles (NPs) in aqueous solutions. The sensor array consists of five different cross-reactive chemoresponsive dyes, whose visible absorbances change in response to their interactions with NPs. Although no single dye is specific for any one NP, the pattern of color changes for all dyes provides a unique molecular fingerprint for each type of NP studied. Based on the responses of various dyes, a semiquantitative determination of concentration of each type of NP could also be accomplished with excellent sensitivity (<100 ng/mL). A variety of chemically distinct NPs were unambiguously identified using a standard chemometric approaches, including gold nanospheres (2 through 40 nm diameter), gold nanorods (2.4 and 3.5 aspect ratios), and multifunctional carbon nanospheres without errors in 112 trials. This colorimetric approach may pave the way for a fast, reliable, and inexpensive method to detect nanopollution and to characterize the physiochemical properties of NPs. Show less

The elucidation of factors that activate the regeneration of the adult mammalian heart is of major scientific and therapeutic importance. Here we found that epicardial cells contain a potent cardiogenic activity identified as follistatin-like 1 (Fstl1). Epicardial Fstl1 declines following myocardial infarction and is replaced by myocardial expression. Myocardial Fstl1 does not promote regeneration, either basally or upon transgenic overexpression. Application of the human Fstl1 protein (FSTL1)… Show more

The elucidation of factors that activate the regeneration of the adult mammalian heart is of major scientific and therapeutic importance. Here we found that epicardial cells contain a potent cardiogenic activity identified as follistatin-like 1 (Fstl1). Epicardial Fstl1 declines following myocardial infarction and is replaced by myocardial expression. Myocardial Fstl1 does not promote regeneration, either basally or upon transgenic overexpression. Application of the human Fstl1 protein (FSTL1) via an epicardial patch stimulates cell cycle entry and division of pre-existing cardiomyocytes, improving cardiac function and survival in mouse and swine models of myocardial infarction. The data suggest that the loss of epicardial FSTL1 is a maladaptive response to injury, and that its restoration would be an effective way to reverse myocardial death and remodelling following myocardial infarction in humans. Show less

Nanoparticle-mediated sustained delivery of therapeutics is one of the highly effective and increasingly utilized applications of nanomedicine. Here, we report the development and application of a drug delivery system consisting of polyethylene glycol (PEG)-conjugated liposomal nanoparticles as an efficient in vivo delivery approach for [Pyr1]-apelin-13 polypeptide. Apelin is an adipokine that regulates a variety of biological functions including cardiac hypertrophy and hypertrophy-induced… Show more

Nanoparticle-mediated sustained delivery of therapeutics is one of the highly effective and increasingly utilized applications of nanomedicine. Here, we report the development and application of a drug delivery system consisting of polyethylene glycol (PEG)-conjugated liposomal nanoparticles as an efficient in vivo delivery approach for [Pyr1]-apelin-13 polypeptide. Apelin is an adipokine that regulates a variety of biological functions including cardiac hypertrophy and hypertrophy-induced heart failure. The clinical use of apelin has been greatly impaired by its remarkably short half-life in circulation. Here, we investigate whether [Pyr1]-apelin-13 encapsulation in liposome nanocarriers, conjugated with PEG polymer on their surface, can prolong apelin stability in the blood stream and potentiate apelin beneficial effects in cardiac function. Atomic force microscopy and dynamic light scattering were used to assess the structure and size distribution of drug-laden nanoparticles. [Pyr1]-apelin-13 encapsulation in PEGylated liposomal nanocarriers resulted in sustained and extended drug release both in vitro and in vivo. Moreover, intraperitoneal injection of [Pyr1]-apelin-13 nanocarriers in a mouse model of pressure-overload induced heart failure demonstrated a sustainable long-term effect of [Pyr1]-apelin-13 in preventing cardiac dysfunction. We concluded that this engineered nanocarrier system can serve as a delivery platform for treating heart injuries through sustained bioavailability of cardioprotective therapeutics. Show less

Two decades of the amyloid-β (Aβ) hypothesis in Alzheimer’s disease (AD) and the prominence of Aβ-targeting strategies have yet to meet the levels of original expectation. Disappointing results in numerous Phase II/III studies have called for a re-examination of the validity of the Aβ-targeting approaches as an intervention strategy in AD. The mid-life onset of chronic conditions (e.g., hypertension, diabetes, insulin intolerance, and depression nominated as risk factors for the later… Show more

Two decades of the amyloid-β (Aβ) hypothesis in Alzheimer’s disease (AD) and the prominence of Aβ-targeting strategies have yet to meet the levels of original expectation. Disappointing results in numerous Phase II/III studies have called for a re-examination of the validity of the Aβ-targeting approaches as an intervention strategy in AD. The mid-life onset of chronic conditions (e.g., hypertension, diabetes, insulin intolerance, and depression nominated as risk factors for the later development of AD) points to the possibility that each condition could involve mechanisms, which while relatively modest over a short-term, could have significant accumulative effects. What may also not be fully appreciated is that a number of these conditions involve potential disturbances to multivalent cations (MC) levels through various mechanisms such as autophagy, oxidative stress, and apoptosis. Furthermore, some MCs have intimate associations with the mechanisms by which Aβ pathology manifests. Considering various lines of evidence and incorporating statistical analysis on Disability–Adjusted Life Years (DALYs) data of both causes of and prevalence of multifactorial risk factors in different world regions, we propose an MC hypothesis for AD. More specifically, we suggest that MC imbalance marks many chronic conditions and because of their involvement with Aβ pathology, could reflect that Aβ may be a vital manifestation and marker of underlying MC imbalance. Thus, careful targeting of MC imbalance may provide an alternative or complementary interventional approach to current Aβ treatment strategies. Show less

It is well recognized that the primary interaction of most biological environments with nanoparticles (NPs) is strongly influenced by a long-lived (“hard”) protein corona that surrounds the NP and remains strongly adsorbed to its surface. The amount and composition of associated proteins in the corona adsorbed onto the NPs is related to several important factors, including the physicochemical properties of the NPs and the composition of the protein solution. Here, for the first time, it is… Show more

It is well recognized that the primary interaction of most biological environments with nanoparticles (NPs) is strongly influenced by a long-lived (“hard”) protein corona that surrounds the NP and remains strongly adsorbed to its surface. The amount and composition of associated proteins in the corona adsorbed onto the NPs is related to several important factors, including the physicochemical properties of the NPs and the composition of the protein solution. Here, for the first time, it is shown that plasmonic heat induction (by laser activation) leads to significant changes in the composition of the hard protein corona adsorbed on low aspect ratio gold nanorods. Using mass spectrometry, several proteins in the corona were identified whose concentrations change most substantially as a result of photoinduced (plasmonic) heating versus simple thermal heating. Molecular modeling suggests that the origin of these changes in protein adsorption may be the result of protein conformational changes in response to much higher local temperatures that occur near the gold nanorods during photoinduced, plasmonic heating. These results may define new applications in vivo for NPs with hyperthermia capability and better define the likely interactions of cells with NPs after plasmonic heating. Potential changes in the protein corona following hyperthermia treatment may influence the final biological fate of plasmonic NPs in clinical applications and help elucidate safety considerations for hyperthermia applications. Show less

Bioinspired materials can mimic the stem cell environment and modulate stem cell differentiation and proliferation. In this study, biomimetic micro/nanoenvironments were fabricated by cell-imprinted substrates based on mature human keratinocyte morphological templates. The data obtained from atomic force microscopy and field emission scanning electron microscopy revealed that the keratinocyte-cell-imprinted poly(dimethylsiloxane) casting procedure could imitate the surface morphology of the… Show more

Bioinspired materials can mimic the stem cell environment and modulate stem cell differentiation and proliferation. In this study, biomimetic micro/nanoenvironments were fabricated by cell-imprinted substrates based on mature human keratinocyte morphological templates. The data obtained from atomic force microscopy and field emission scanning electron microscopy revealed that the keratinocyte-cell-imprinted poly(dimethylsiloxane) casting procedure could imitate the surface morphology of the plasma membrane, ranging from the nanoscale to the macroscale, which may provide the required topographical cell fingerprints to induce differentiation. Gene expression levels of the genes analyzed (involucrin, collagen type I, and keratin 10) together with protein expression data showed that human adipose-derived stem cells (ADSCs) seeded on these cell-imprinted substrates were driven to adopt the specific shape and characteristics of keratinocytes. The observed morphology of the ADSCs grown on the keratinocyte casts was noticeably different from that of stem cells cultivated on the stem-cell-imprinted substrates. Since the shape and geometry of the nucleus could potentially alter the gene expression, we used molecular dynamics to probe the effect of the confining geometry on the chain arrangement of simulated chromatin fibers in the nuclei. The results obtained suggested that induction of mature cell shapes onto stem cells can influence nucleus deformation of the stem cells followed by regulation of target genes. This might pave the way for a reliable, efficient, and cheap approach of controlling stem cell differentiation toward skin cells for wound healing applications. Show less

Smart nanoenvironments were obtained by cell-imprinted substrates based on mature and dedifferentiated chondrocytes as templates. Rabbit adipose derived mesenchymal stem cells (ADSCs) seeded on these cell-imprinted substrates were driven to adopt the specific shape (as determined in terms of cell morphology) and molecular characteristics (as determined in terms of gene expression) of the cell types which had been used as template for the cell-imprinting. This method might pave the way for a… Show more

Smart nanoenvironments were obtained by cell-imprinted substrates based on mature and dedifferentiated chondrocytes as templates. Rabbit adipose derived mesenchymal stem cells (ADSCs) seeded on these cell-imprinted substrates were driven to adopt the specific shape (as determined in terms of cell morphology) and molecular characteristics (as determined in terms of gene expression) of the cell types which had been used as template for the cell-imprinting. This method might pave the way for a reliable, efficient, and cheap way of controlling stem cell differentiation. Data also suggest that besides residual cellular fragments, which are presented on the template surface, the imprinted topography of the templates plays a role in the differentiation of the stem cells. Show less

Superparamagnetic iron oxide nanoparticles (SPIONs) are recognized as promising nanodiagnostic materials due to their biocompatibility, unique magnetic properties, and their application as multimodal contrast agents. As coated SPIONs have potential use in the diagnosis and treatment of various brain diseases such as Alzheimer’s, a comprehensive understanding of their interactions with Aβ and other amyloidogenic proteins is essential prior to their clinical application. Here we demonstrate the… Show more

Superparamagnetic iron oxide nanoparticles (SPIONs) are recognized as promising nanodiagnostic materials due to their biocompatibility, unique magnetic properties, and their application as multimodal contrast agents. As coated SPIONs have potential use in the diagnosis and treatment of various brain diseases such as Alzheimer’s, a comprehensive understanding of their interactions with Aβ and other amyloidogenic proteins is essential prior to their clinical application. Here we demonstrate the effect of thickness and surface charge of the coating layer of SPIONs on the kinetics of fibrillation of Aβ in aqueous solution. A size and surface area dependent “dual” effect on Aβ fibrillation was observed. While lower concentrations of SPIONs inhibited fibrillation, higher concentrations increased the rate of Aβ fibrillation. With respect to coating charge, it is evident that the positively charged SPIONs are capable of promoting fibrillation at significantly lower particle concentrations compared with negatively charged or uncharged SPIONs. This suggests that in addition to the presence of particles, which affect the concentration of monomeric protein in solution (and thereby the nucleation time), there are also effects of binding on the protein conformation. Show less

Upon incorporation of nanoparticles (NPs) into the body, they are exposed to biological fluids, and their interaction with the dissolved biomolecules leads to the formation of the so-called protein corona on the surface of the NPs. The composition of the corona plays a crucial role in the biological fate of the NPs. While the effects of various physicochemical parameters on the composition of the corona have been explored in depth, the role of temperature upon its formation has received much… Show more

Upon incorporation of nanoparticles (NPs) into the body, they are exposed to biological fluids, and their interaction with the dissolved biomolecules leads to the formation of the so-called protein corona on the surface of the NPs. The composition of the corona plays a crucial role in the biological fate of the NPs. While the effects of various physicochemical parameters on the composition of the corona have been explored in depth, the role of temperature upon its formation has received much less attention. In this work, we have probed the effect of temperature on the protein composition on the surface of a set of NPs with various surface chemistries and electric charges. Our results indicate that the degree of protein coverage and the composition of the adsorbed proteins on the NPs’ surface depend on the temperature at which the protein corona is formed. Also, the uptake of NPs is affected by the temperature. Temperature is, thus, an important parameter that needs to be carefully controlled in quantitative studies of bionano interactions. Show less

When nanoparticles (NPs) are exposed to the biological environment, their surfaces become covered with proteins and biomolecules (e.g. lipids). Here, we report that this protein coating, or corona, reduces the targeting capability of surface engineered NPs by screening the active sites of the targeting ligands.

Antibacterial agents are very important in the textile industry, water disinfection, medicine, and food packaging. Organic compounds used for disinfection have some disadvantages, including toxicity to the human body, therefore, the interest in inorganic disinfectants such as metal oxide nanoparticles (NPs) is increasing. This review focuses on the properties and applications of inorganic nanostructured materials and their surface modifications, with good antimicrobial activity. Such improved… Show more

Antibacterial agents are very important in the textile industry, water disinfection, medicine, and food packaging. Organic compounds used for disinfection have some disadvantages, including toxicity to the human body, therefore, the interest in inorganic disinfectants such as metal oxide nanoparticles (NPs) is increasing. This review focuses on the properties and applications of inorganic nanostructured materials and their surface modifications, with good antimicrobial activity. Such improved antibacterial agents locally destroy bacteria, without being toxic to the surrounding tissue. We also provide an overview of opportunities and risks of using NPs as antibacterial agents. In particular, we discuss the role of different NP materials. Show less

Nanoscience has matured significantly during the last decade as it has transitioned from bench top science to applied technology. Presently, nanomaterials are used in a wide variety of commercial products such as electronic components, sports equipment, sun creams and biomedical applications. There are few studies of the long-term consequences of nanoparticles on human health, but governmental agencies, including the United States National Institute for Occupational Safety and Health and… Show more

Nanoscience has matured significantly during the last decade as it has transitioned from bench top science to applied technology. Presently, nanomaterials are used in a wide variety of commercial products such as electronic components, sports equipment, sun creams and biomedical applications. There are few studies of the long-term consequences of nanoparticles on human health, but governmental agencies, including the United States National Institute for Occupational Safety and Health and Japan's Ministry of Health, have recently raised the question of whether seemingly innocuous materials such as carbon-based nanotubes should be treated with the same caution afforded known carcinogens such as asbestos. Since nanomaterials are increasing a part of everyday consumer products, manufacturing processes, and medical products, it is imperative that both workers and end-users be protected from inhalation of potentially toxic NPs. It also suggests that NPs may need to be sequestered into products so that the NPs are not released into the atmosphere during the product's life or during recycling. Further, non-inhalation routes of NP absorption, including dermal and medical injectables, must be studied in order to understand possible toxic effects. Fewer studies to date have addressed whether the body can eventually eliminate nanomaterials to prevent particle build-up in tissues or organs. This critical review discusses the biophysicochemical properties of various nanomaterials with emphasis on currently available toxicology data and methodologies for evaluating nanoparticle toxicity. Show less

Until now, the results of nanotoxicology research have shown that the interactions between nanoparticles (NPs) and cells are remarkably complex. In order to get a deep understanding of the NP-cell interactions, scientists have focused on the physicochemical effects. However, there are still considerable debates about the regulation of nanomaterials and the reported results are usually in contradictions. Here, we are going to introduce the potential key reasons for these conflicts. In this case,… Show more

Until now, the results of nanotoxicology research have shown that the interactions between nanoparticles (NPs) and cells are remarkably complex. In order to get a deep understanding of the NP-cell interactions, scientists have focused on the physicochemical effects. However, there are still considerable debates about the regulation of nanomaterials and the reported results are usually in contradictions. Here, we are going to introduce the potential key reasons for these conflicts. In this case, modification of conventional in vitro toxicity assays, is one of the crucial ignored matter in nanotoxicological sciences. More specifically, the conventional methods neglect important factors such as the sedimentation of NPs and absorption of proteins and other essential biomolecules onto the surface of NPs. Another ignored matter in nanotoxicological sciences is the effect of cell “vision” (i.e., cell type). In order to show the effects of these ignored subjects, we probed the effect of superparamagnetic iron oxide NPs (SPIONs), with various surface chemistries, on various cell lines. We found thatthe modification of conventional toxicity assays and the consideration of the “cell vision” concept are crucial matters to obtain reliable, and reproducible nanotoxicology data. These new concepts offer a suitable way to obtain a deep understanding on the cell-NP interactions. In addition, by consideration of these ignored factors, the conflict of future toxicological reports would be significantly decreased. Show less

The combination of patients with poor immune system, prolonged exposure to anti-infective drugs, and cross-infection has given rise to nosocomial infections with highly resistant pathogens, which is going to be a growing threat so termed “antibiotic resistance”. Due to their significant antimicrobial activity, silver nanoparticles are recognized as a promising candidate to fight against resistant pathogens; however, there are two major shortcomings with these nanoparticles. First, the silver… Show more

The combination of patients with poor immune system, prolonged exposure to anti-infective drugs, and cross-infection has given rise to nosocomial infections with highly resistant pathogens, which is going to be a growing threat so termed “antibiotic resistance”. Due to their significant antimicrobial activity, silver nanoparticles are recognized as a promising candidate to fight against resistant pathogens; however, there are two major shortcomings with these nanoparticles. First, the silver nanoparticles are highly toxic to the healthy cells; second, due to the protection offered by the biofilm mode of growth, the silver nanoparticles cannot eradicate bacterial biofilms. In order to overcome these limitations, this study introduces a new class of engineered multimodal nanoparticles comprising a magnetic core and a silver ring with a ligand gap. The results indicated promising capability of the designed multimodal nanoparticles for high-yield antibacterial effects and eradication of bacterial biofilms, while the particles were completely compatible with the cells. Utilizing a gold ring as an intermediate coating on the produced nanoparticles may exploit new opportunities for theranosis applications. This will require special consideration in future works. Show less

The understanding of the interactions between nanomaterials and proteins is of extreme importance in medicine. In a biological fluid, proteins can adsorb and associate with nanoparticles, which can have significant impact on the biological behavior of the proteins and the nanoparticles. We report here on the interactions of iron saturated human transferrin protein with both bare and polyvinyl alcohol coated superparamagnetic iron oxide nanoparticles (SPIONs). The exposure of human transferrin… Show more

The understanding of the interactions between nanomaterials and proteins is of extreme importance in medicine. In a biological fluid, proteins can adsorb and associate with nanoparticles, which can have significant impact on the biological behavior of the proteins and the nanoparticles. We report here on the interactions of iron saturated human transferrin protein with both bare and polyvinyl alcohol coated superparamagnetic iron oxide nanoparticles (SPIONs). The exposure of human transferrin to SPIONs results in the release of iron, which changes the main function of the protein, which is the transport of iron among cells. After removal of the magnetic nanoparticles, the original protein conformation is not recovered, indicating irreversible changes in transferrin conformation: from a compact to an open structure. Show less

Due to their unique magnetic properties, excellent biocompatibility as well as multi-purpose biomedical potential (e.g., applications in cancer therapy and general drug delivery), superparamagnetic iron oxide nanoparticles (SPIONs) are attracting increasing attention in both pharmaceutical and industrial communities. The precise control of the physiochemical properties of these magnetic systems is crucial for hyperthermia applications, as the induced heat is highly dependent on these… Show more

Due to their unique magnetic properties, excellent biocompatibility as well as multi-purpose biomedical potential (e.g., applications in cancer therapy and general drug delivery), superparamagnetic iron oxide nanoparticles (SPIONs) are attracting increasing attention in both pharmaceutical and industrial communities. The precise control of the physiochemical properties of these magnetic systems is crucial for hyperthermia applications, as the induced heat is highly dependent on these properties. In this review, the limitations and recent advances in the development of superparamagnetic iron oxide nanoparticles for hyperthermia are presented. Show less

At present, nanoparticles are used for various biomedical applications where they facilitate laboratory diagnostics and therapeutics. More specifically for drug delivery purposes, the use of nanoparticles is attracting increasing attention due to their unique capabilities and their negligible side effects not only in cancer therapy but also in the treatment of other ailments. Among all types of nanoparticles, biocompatible superparamagnetic iron oxide nanoparticles (SPIONs) with proper surface… Show more

At present, nanoparticles are used for various biomedical applications where they facilitate laboratory diagnostics and therapeutics. More specifically for drug delivery purposes, the use of nanoparticles is attracting increasing attention due to their unique capabilities and their negligible side effects not only in cancer therapy but also in the treatment of other ailments. Among all types of nanoparticles, biocompatible superparamagnetic iron oxide nanoparticles (SPIONs) with proper surface architecture and conjugated targeting ligands/proteins have attracted a great deal of attention for drug delivery applications.

This review covers recent advances in the development of SPIONs together with their possibilities and limitations from fabrication to application in drug delivery. In addition, the state-of-the-art synthetic routes and surface modification of desired SPIONs for drug delivery purposes are described. Show less

In recent years, the production of nanoparticles (NPs) and exploration of their unusual properties have attracted the attention of physicists, chemists, biologists and engineers. Interest in NPs arises from the fact that the mechanical, chemical, electrical, optical, magnetic, electro-optical and magneto-optical properties of these particles are different from their bulk properties and depend on the particle size. There are numerous areas where nanoparticulate systems are of scientific and… Show more

In recent years, the production of nanoparticles (NPs) and exploration of their unusual properties have attracted the attention of physicists, chemists, biologists and engineers. Interest in NPs arises from the fact that the mechanical, chemical, electrical, optical, magnetic, electro-optical and magneto-optical properties of these particles are different from their bulk properties and depend on the particle size. There are numerous areas where nanoparticulate systems are of scientific and technological interest, particularly in biomedicine where the emergence of NPs with specific properties (e.g. magnetic and fluorescence) for contrast agents can lead to advancing the understanding of biological processes at the biomolecular level. This review will cover a full description of the physics of various imaging methods, including MRI, optical techniques, X-rays and CT. In addition, the effect of NPs on the improvement of the mentioned non-invasive imaging methods will be discussed together with their advantages and disadvantages. A detailed discussion will also be provided on the recent advances in imaging agents, such as fluorescent dye-doped silica NPs, quantum dots, gold- and engineered polymeric-NPs, superparamagnetic iron oxide NPs (SPIONs), and multimodal NPs (i.e. nanomaterials that are active in both MRI and optical methods), which are employed to overcome many of the limitations of conventional contrast agents (e.g. gadolinium). Show less

In the last few decades, nanoparticles (NPs) have been recognized as promising candidates for starting a new revolution in science and technology due to their unusual properties, attracting the attention of physicists, chemists, biologists, and engineers. The aim of this study is to evaluate the toxicities (at both cellular and molecular levels) of three forms of superparamagnetic iron oxide nanoparticles (SPIONs) of various surface chemistries (COOH, plain, and NH2) through the comparison with… Show more

In the last few decades, nanoparticles (NPs) have been recognized as promising candidates for starting a new revolution in science and technology due to their unusual properties, attracting the attention of physicists, chemists, biologists, and engineers. The aim of this study is to evaluate the toxicities (at both cellular and molecular levels) of three forms of superparamagnetic iron oxide nanoparticles (SPIONs) of various surface chemistries (COOH, plain, and NH2) through the comparison with gene expression patterns of three cell types (i.e., human heart, brain, and kidney). For this purpose, both an MTT assay and a DNA microarray analysis were applied in three human cell lines—HCM (heart), BE-2-C (brain), and 293T (kidney)—under the exposure to SPIONs-COOH, SPIONs-NH2, and bare SPIONs. The specific gene alteration and hierarchical clustering revealed that SPIONs-COOH altered genes associated with cell proliferative responses due to their reactive oxygen species (ROS) properties. It was also found that the cell type can have quite a significant role in the definition of suitable pathways for detoxification of NPs, which has deep implications for the safe and high yield design of NPs for biomedical applications and will require serious consideration in the future. Show less

Superparamagnetic iron oxide nanoparticles (SPIONs) are increasingly used in medical applications, such as targeting delivery and imaging. In the future, patients are more likely to be exposed to pharmaceutical products containing such particles. The study of toxicity of SPIONs has become of great importance in recent years, although the published data in this arena is limited. The aim of the present work is to investigate the cytotoxicity of SPIONs and the effect of the particles on the cell… Show more

Superparamagnetic iron oxide nanoparticles (SPIONs) are increasingly used in medical applications, such as targeting delivery and imaging. In the future, patients are more likely to be exposed to pharmaceutical products containing such particles. The study of toxicity of SPIONs has become of great importance in recent years, although the published data in this arena is limited. The aim of the present work is to investigate the cytotoxicity of SPIONs and the effect of the particles on the cell medium components. For this purpose, uncoated and polyvinyl alcohol (PVA) coated SPIONs with narrow size distribution were synthesized via a well-known coprecipitation method. The mouse fibroblast cell line L929 was exposed to SPIONs to probe the toxicity of magnetic nanoparticles during the bio application. Changes to the cell medium caused by SPIONs were analyzed with zeta potential measurements, ultraviolet visible spectroscopy (UV/vis) and the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide (MTT) assay. It is observed that gas vesicles are formed in SPION-treated cells. Toxicity is conventionally explained by changes in the DMEM's pH and composition due to the tendency of SPIONs to interact with biomolecules. A new procedure is proposed to examine the in vitro toxicity of nanoparticles in a more rigorous manner, which gives an improvement in the relationship between in vivo and in vitro toxicity studies. Show less

The performance of nanoparticles for biomedical applications is often assessed by their narrow size distribution, suitable magnetic saturation and low toxicity effects. In this work, superparamagnetic iron oxide nanoparticles (SPIONs) with different size, shape and saturation magnetization levels were synthesized via a co-precipitation technique using ferrous salts with a Fe3+/Fe2+ mole ratio equal to 2. A parametric study is conducted, based on a uniform design-of-experiments methodology and a… Show more

The performance of nanoparticles for biomedical applications is often assessed by their narrow size distribution, suitable magnetic saturation and low toxicity effects. In this work, superparamagnetic iron oxide nanoparticles (SPIONs) with different size, shape and saturation magnetization levels were synthesized via a co-precipitation technique using ferrous salts with a Fe3+/Fe2+ mole ratio equal to 2. A parametric study is conducted, based on a uniform design-of-experiments methodology and a critical polymer/iron mass ratio (r-ratio) for obtaining SPION with narrow size distribution, suitable magnetic saturation, and optimum biocompatibility is identified. Polyvinyl alcohol (PVA) has been used as the nanoparticle coating material, owing to its low toxicity. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay is used to investigate the cell biocompatibility/toxicity effects of the samples. From the MTT assay results, it is observed that the biocompatibility of the nanoparticles, based on cell viabilities, can be enhanced by increasing the r-ratio, regardless of the stirring rate. This effect is mainly due to the growth of the particle hydrodynamic size, causing lower cell toxicity effects.
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Superparamagnetic iron oxide nanoparticles with proper surface coatings are increasingly being evaluated for clinical applications such as hyperthermia, drug delivery, magnetic resonance imaging, transfection, and cell/protein separation. To enhance the applicability of magnetic nanoparticles, two main problems must be overcome. First, as the drug coats the particle surface, a significant portion of it is quickly released upon injection (burst effect). Therefore, only small amounts of the drug… Show more

Superparamagnetic iron oxide nanoparticles with proper surface coatings are increasingly being evaluated for clinical applications such as hyperthermia, drug delivery, magnetic resonance imaging, transfection, and cell/protein separation. To enhance the applicability of magnetic nanoparticles, two main problems must be overcome. First, as the drug coats the particle surface, a significant portion of it is quickly released upon injection (burst effect). Therefore, only small amounts of the drug reach the specific site after, for example, magnetic drug targeting. Second, once the surface-derivatized nanoparticles are inside the cells, the coating is likely digested, leaving the bare particles exposed to other cellular components and organelles, thereby potentially influencing the overall integrity of the cells. To overcome these two shortcomings, iron oxide nanoparticles with cross-linked poly (ethylene glycol)-co-fumarate (PEGF) coating were synthesized. The obtained material was highly stable and easy to handle due to the well-dispersed magnetic nanoparticles. Using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, even very high concentrations of the novel magnetic nanoparticles were found to be biocompatible. To investigate if the coating could reduce the burst effect, nanoparticles were prepared by incorporating the anticancer drug tamoxifen. The cross-linked PEGF coating reduced the burst effect rate by 21% in comparison with the noncross-linked tamoxifen nanoparticles. Our results suggest that nanoparticles with coatings based on cross-linked unsaturated aliphatic polyesters are potentially useful to develop novel carriers for drug and gene delivery applications. Show less

Superparamagnetic iron oxide nanoparticles (SPION) are being increasingly used in various biomedical applications such as hyperthermia, cell and protein separation, enhancing resolution of magnetic resonance imaging, and drug delivery. However, the toxicity data for SPION are limited. In this study, uncoated and single polyvinyl alcohol coated SPION with high chemical reactivity (due to the bigger surface area) were synthesized using a coprecipitation method. Cytotoxicity of these magnetic… Show more

Superparamagnetic iron oxide nanoparticles (SPION) are being increasingly used in various biomedical applications such as hyperthermia, cell and protein separation, enhancing resolution of magnetic resonance imaging, and drug delivery. However, the toxicity data for SPION are limited. In this study, uncoated and single polyvinyl alcohol coated SPION with high chemical reactivity (due to the bigger surface area) were synthesized using a coprecipitation method. Cytotoxicity of these magnetic nanoparticles and their ability to cause arrest in cell life-cycles was investigated. Interaction of these nanoparticles with adhesive mouse fibroblast cell line (L929) was probed using MTT assay. High concentrations of coated SPION (i.e., 100, 200, and 400 mM) demonstrated high cell viability following an exposure to the cells. Treated cells, via coated magnetic nanoparticles, did not showed evident necrosis, apoptosis (via propidium iodide staining), or cell cycle arrest in moderate concentration, i.e., 200 mM. However, the coated nanoparticles at the highest concentration (400 mM) caused both apoptosis and cell cycle arrest in G1 phase, possibly due to the irreversible DNA damage and repair of oxidative DNA lesions. Uncoated nanoparticles showed significant apoptosis amount at the highest concentration. The mentioned damaged occurred because of proteins attachments to the surface of nanoparticles, leading to the formation of protein “corona” on the shell of magnetic particles. The associations of proteins on the surface of nanoparticles were confirmed by UV/Vis spectroscopy. Finally, the effect of particle surface (i.e., uncoated and coated) on the cell cycle was studied. Show less

Superparamagnetic iron oxide nanoparticles (SPION) with narrow size distribution and stabilized by polyvinyl alcohol (PVA) were synthesized. The particles were prepared by a coprecipitation technique using ferric and ferrous salts with a molar Fe3+/Fe2+ ratio of 2. Using a design of experiments (DOE) approach, the effect of different synthesis parameters (stirring rate and base molarity) on the structure, morphology, saturation magnetization, purity, size, and size distribution of the… Show more

Superparamagnetic iron oxide nanoparticles (SPION) with narrow size distribution and stabilized by polyvinyl alcohol (PVA) were synthesized. The particles were prepared by a coprecipitation technique using ferric and ferrous salts with a molar Fe3+/Fe2+ ratio of 2. Using a design of experiments (DOE) approach, the effect of different synthesis parameters (stirring rate and base molarity) on the structure, morphology, saturation magnetization, purity, size, and size distribution of the synthesized magnetite nanoparticles was studied by various analysis techniques including X-ray powder diffraction (XRD), thermogravimetric analysis (TGA) with differential scanning calorimetry (DSC) measurements, vibrating-sample magnetometer (VSM), transmission electron microscopy (TEM), UV−visible, and Fourier transform infrared (FT-IR) spectrometer. PVA not only stabilized the colloid but also played a role in preventing further growth of SPION followed by the formation of large agglomerates by chemisorption on the surface of particles. A rich behavior in particle size, particle formation, and super paramagnetic properties is observed as a function of molarity and stirring conditions. The particle size and the magnetic properties as well as particle shape and aggregation (individual nanoparticles, magnetic beads, and magnetite colloidal nanocrystal clusters (CNCs)) are found to be influenced by changes in the stirring rate and the base molarity. The formation of magnetic beads results in a decrease in the saturation magnetization, while CNCs lead to an increase in saturation magnetization. On the basis of the DOE methodology and the resulting 3-D response surfaces for particle size and magnetic properties, it is shown that optimum regions for stirring rate and molarity can be obtained to achieve coated SPION with desirable size, purity, magnetization, and shape. Show less

Nanoparticles (NPs) have emerged as one of the most innovative and promising application in agriculture. Since plants are recognized as essential component of all ecosystems, the effects of NPs on plants may pave a new insight to the ecosystems. Here, uptake and translocation of superparamagnetic iron oxide NPs (SPIONs), with various surface charges, on soybean has been probed; in addition, the effects of SPIONs on variations of chlorophyll, in hydroponic condition, together with their ability… Show more

Nanoparticles (NPs) have emerged as one of the most innovative and promising application in agriculture. Since plants are recognized as essential component of all ecosystems, the effects of NPs on plants may pave a new insight to the ecosystems. Here, uptake and translocation of superparamagnetic iron oxide NPs (SPIONs), with various surface charges, on soybean has been probed; in addition, the effects of SPIONs on variations of chlorophyll, in hydroponic condition, together with their ability for reduction of iron deficiency chlorosis were explored. We find that SPIONs, which were entered and translocated in the soybean, increased chlorophyll levels, with no trace of toxicity. Furthermore, it was found that physicochemical characteristics of the SPIONs had a crucial role on the enhancement of chlorophyll content in subapical leaves of soybean. The equivalent ratio of chlorophyll a to b, in all treatments with conventional growth medium iron chelate and SPIONs (as iron source), indicated no significant difference on the photosynthesis efficiency. Finally, it was observed that the effect of SPIONs on the soybean chlorophyll content may have influence on both biochemical and enzymatic efficiency in different stages of the photosynthesis reactions. Show less

A comprehensive review is presented on the development and state of the art of colorimetric and fluorometric sensor arrays. Optical arrays based on chemoresponsive colorants (dyes and nanoporous pigments) probe the chemical reactivity of analytes, rather than their physical properties. This provides a high dimensionality to chemical sensing that permits high sensitivity (often down to ppb levels), impressive discrimination among very similar analytes and exquisite fingerprinting of extremely… Show more

A comprehensive review is presented on the development and state of the art of colorimetric and fluorometric sensor arrays. Optical arrays based on chemoresponsive colorants (dyes and nanoporous pigments) probe the chemical reactivity of analytes, rather than their physical properties. This provides a high dimensionality to chemical sensing that permits high sensitivity (often down to ppb levels), impressive discrimination among very similar analytes and exquisite fingerprinting of extremely similar mixtures over a wide range of analyte types, both in the gas and liquid phases. Show less

Regeneration of the damaged myocardium is one of the most challenging fronts in the field of tissue engineering due to the limited capacity of adult heart tissue to heal and to the mechanical and structural constraints of the cardiac tissue. In this study we demonstrate that an engineered acellular scaffold comprising type I collagen, endowed with specific physiomechanical properties, improves cardiac function when used as a cardiac patch following myocardial infarction. Patches were grafted… Show more

Regeneration of the damaged myocardium is one of the most challenging fronts in the field of tissue engineering due to the limited capacity of adult heart tissue to heal and to the mechanical and structural constraints of the cardiac tissue. In this study we demonstrate that an engineered acellular scaffold comprising type I collagen, endowed with specific physiomechanical properties, improves cardiac function when used as a cardiac patch following myocardial infarction. Patches were grafted onto the infarcted myocardium in adult murine hearts immediately after ligation of left anterior descending artery and the physiological outcomes were monitored by echocardiography, and by hemodynamic and histological analyses four weeks post infarction. In comparison to infarcted hearts with no treatment, hearts bearing patches preserved contractility and significantly protected the cardiac tissue from injury at the anatomical and functional levels. This improvement was accompanied by attenuated left ventricular remodeling, diminished fibrosis, and formation of a network of interconnected blood vessels within the infarct. Histological and immunostaining confirmed integration of the patch with native cardiac cells including fibroblasts, smooth muscle cells, epicardial cells, and immature cardiomyocytes. In summary, an acellular biomaterial with specific biomechanical properties promotes the endogenous capacity of the infarcted myocardium to attenuate remodeling and improve heart function following myocardial infarction. Show less