Publications by authors named "Morteza Mahmoudi"

206 Publications

Protein corona profile of graphene oxide allows detection of glioblastoma multiforme using a simple one-dimensional gel electrophoresis technique: a proof-of-concept study.

Biomater Sci 2021 May 21. Epub 2021 May 21.

Nanodelivery Lab, Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.

Glioblastoma multiforme (GBM) is the most aggressive form of gliomas. The development of supplementary approaches for glioblastoma diagnosis, limited to imaging techniques and tissue biopsies so far, is a necessity of clinical relevance. In this context, nanotechnology might afford tools to enable early diagnosis. Upon exposure to biological media, nanoparticles are coated with a layer of proteins, the protein corona (PC), whose composition is individual and personalized. Here we show that the PC of graphene oxide nanosheets has a capacity to detect GBM using a simple one-dimensional gel electrophoresis technique. In a range of molecular weights between 100 and 120 kDa, the personalized PC from GBM patients is completely discernible from that of healthy donors and that of cancer patients affected by pancreatic adenocarcinoma and colorectal cancer. Using tandem mass spectrometry, we found that inter-alpha-trypsin inhibitor (ITI) heavy chain H4 is enriched in the PC of all tested individuals but not in the GBM patients. Overall, if confirmed on a larger cohort series, this approach could be advantageous at the first level of investigation to decide whether to carry out more invasive analyses and/or to follow up patients after surgery and/or pharmacological treatment.
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http://dx.doi.org/10.1039/d1bm00488cDOI Listing
May 2021

Sex as an important factor in nanomedicine.

Nat Commun 2021 05 20;12(1):2984. Epub 2021 May 20.

Department of Radiology and Precision Health Program, Michigan State University, East Lansing, MI, US.

Nanomedicine has demonstrated substantial potential to improve the quality and efficacy of healthcare systems. Although the promise of nanomedicine to transform conventional medicine is evident, significant numbers of therapeutic nanomedicine products have failed in clinical trials. Most studies in nanomedicine have overlooked several important factors, including the significance of sex differences at various physiological levels. This report attempts to highlight the importance of sex in nanomedicine at cellular and molecular level. A more thorough consideration of sex physiology, among other critical variations (e.g., health status of individuals), would enable researchers to design and develop safer and more-efficient sex-specific diagnostic and therapeutic nanomedicine products.
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http://dx.doi.org/10.1038/s41467-021-23230-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170671PMC
May 2021

Special Focus Issue Part I: Functional nanomaterials in cancer therapy.

Nanomedicine (Lond) 2021 05;16(11):879-882

Department of Radiology & Precision Health Program, Michigan State University, 766 Service Road, East Lansing, MI 48824, USA.

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http://dx.doi.org/10.2217/nnm-2021-0150DOI Listing
May 2021

The Possible Role of Sex As an Important Factor in Development and Administration of Lipid Nanomedicine-Based COVID-19 Vaccine.

Mol Pharm 2021 06 13;18(6):2448-2453. Epub 2021 May 13.

Department of Radiology and Precision Health Program, Michigan State University, East Lansing, Michigan 48824, United States.

Nanomedicine has demonstrated a substantial role in vaccine development against severe acute respiratory syndrome coronavirus (SARS-CoV-2 and COVID-19). Although nanomedicine-based vaccines have now been validated in millions of individuals worldwide in phase 4 and tracking of sex-disaggregated data on COVID-19 is ongoing, immune responses that underlie COVID-19 disease outcomes have not been clarified yet. A full understanding of sex-role effects on the response to nanomedicine products is essential to building an effective and unbiased response to the pandemic. Here, we exposed model lipid nanoparticles (LNPs) to whole blood of 18 healthy donors (10 females and 8 males) and used flow cytometry to measure cellular uptake by circulating leukocytes. Our results demonstrated significant differences in the uptake of LNP between male and female natural killer (NK) cells. The results of this proof-of-concept study show the importance of recipient sex as a critical factor which enables researchers to better consider sex in the development and administration of vaccines for safer and more-efficient sex-specific outcomes.
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http://dx.doi.org/10.1021/acs.molpharmaceut.1c00291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130523PMC
June 2021

COVID-19 and Its Global Economic Impact.

Adv Exp Med Biol 2021 ;1318:825-837

Universal Scientific Education and Research Network (USERN), Tehran, Iran.

Pandemics are enormous threats to the world that impact all aspects of our lives, especially the global economy. The COVID-19 pandemic has emerged since December 2019 and has affected the global economy in many ways. As the world becomes more interconnected, the economic impacts of the pandemic become more serious. In addition to increased health expenditures and reduced labor force, the pandemic has hit the supply and demand chain massively and caused trouble for manufacturers who have to fire some of their employees or delay their economic activities to prevent more loss. With the closure of manufacturers and companies and reduced travel rates, usage of oil after the beginning of the pandemic has decreased significantly that was unprecedented in the last 30 years. The mining industry is a critical sector in several developing countries, and the COVID-19 pandemic has hit this industry too. Also, world stock markets declined as investors started to become concerned about the economic impacts of the COVID-19 pandemic. The tourism industry and airlines have also experienced an enormous loss too. The GDP has reduced, and this pandemic will cost the world more than 2 trillion at the end of 2020.
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http://dx.doi.org/10.1007/978-3-030-63761-3_46DOI Listing
May 2021

The role of sex as a biological variable in the efficacy and toxicity of therapeutic nanomedicine.

Adv Drug Deliv Rev 2021 May 4;174:337-347. Epub 2021 May 4.

Department of Radiology and Precision Health Program, Michigan State University, MI, USA; Mary Horrigan Connors Center for Women's Health and Gender Biology, Brigham and Women's Hospital, Harvard Medical School, MA, USA. Electronic address:

Males and females have physiological, hormonal, and genetic differences that can cause different responses to medicinal treatments. The role of sex in the pharmacokinetics and pharmacodynamics of drugs is well established in the literature. However, researchers have yet to robustly and consistently consider the impact of sex differences on the pharmacokinetics and pharmacodynamics of nanomedicine formulations when designing nanomedicine therapeutics and/or constructing clinical trials. In this review, we highlight the physiological and anatomical differences between sexes and discuss how these differences can influence the therapeutic efficacy, side effects, and drug delivery safety of nanomedicine products. A deep understanding of the effects of sex on nano-based drug delivery agents will robustly improve the risk assessment process, resulting in safer formulations, successful clinical translation, and improved therapeutic efficacies for both sexes.
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http://dx.doi.org/10.1016/j.addr.2021.04.028DOI Listing
May 2021

Interdependency of influential parameters in therapeutic nanomedicine.

Expert Opin Drug Deliv 2021 May 12:1-15. Epub 2021 May 12.

Department of Radiology and Precision Health Program, College of Human Medicine, Michigan State University, East Lansing, MI, USA.

Current challenges to successful clinical translation of therapeutic nanomedicine have discouraged many stakeholders, including patients. Significant effort has been devoted to uncovering the reasons behind the less-than-expected success, beyond failures or ineffectiveness, of therapeutic nanomedicine products (e.g. cancer nanomedicine). Until we understand and address the factors that limit the safety and efficacy of NPs, both individually and in combination, successful clinical development will lag.This review highlights the critical roles of interdependent factors affecting the safety and therapeutic efficacy of therapeutic NPs for drug delivery applications.Deep analysis of the current nanomedical literature reveals ahistory of unanticipated complexity by awide range of stakeholders including researchers. In the manufacture of nanomedicines themselves, there have been persistent difficulties with reproducibility and batch-to-batch variation. The unanticipated complexity and interdependency of nano-bio parameters has delayed our recognition of important factors affecting the safety and therapeutic efficacy of nanomedicine products. These missteps have had many factors including our lack of understanding of the interdependency of various factors affecting the biological identity and fate of NPs and biased interpretation of data. All these issues could raise significant concern regarding the reproducibility- or even the validity- of past publications that in turn formed the basis of many clinical trials of therapeutic nanomedicines. Therefore, the individual and combined effects of previously overlooked factors on the safety and therapeutic efficacy of NPs need to be fully considered in nanomedicine reports and product development.
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http://dx.doi.org/10.1080/17425247.2021.1921732DOI Listing
May 2021

Function of arteries and veins in conditions of simulated cardiac arrest.

Bioimpacts 2021 7;11(2):157-164. Epub 2021 Mar 7.

Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, MA, USA.

The study examined the behavior of vasculature in conditions of eliminated cardiac function using mathematical modeling. In addition, we addressed the question of whether the stretch-recoil capability of veins, at least in part accounts for the slower response to simulated cardiac arrest. In the first set of computational experiments, blood flow and pressure patterns in veins and arteries during the first few seconds after cardiac arrest were assessed via a validated multi-scale mathematical model of the whole cardiovascular system, comprising cardiac dynamics, arterial and venous blood flow dynamics, and microcirculation. In the second set of experiments, the effects of stretch-recoil zones of venous vessels with different diameters and velocities on blood velocity and dynamic pressure analyzed using computational fluid dynamics (CFD) modeling. In the first set of experiments, measurement of changes in velocity, dynamic pressure, and fluid flow revealed that the venous system responded to cardiac arrest more slowly compared to the arteries. This disparity might be due to the intrinsic characteristics of the venous system, including stretch-recoil and elastic fiber composition. In the second set of experiments, we attempted to determine the role of the stretch-recoil capability of veins in the slower response to cardiac arrest. During the second set of experiments, we found that this recoil behavior increased dynamic pressure, velocity, and blood flow. The enhancement in dynamic pressure through combining the results from both experiments yielded a 15-40% increase in maximum dynamic pressure due to stretch-recoil, depending on vein diameter under normal conditions. In the situation of cardiac arrest, the vein geometry changes continue, promoting smooth responses of the venous system. Moreover, the importance of such vein behavior in blood displacement may grow as the pressure on the venous side gradually decreases with time. Our experiments suggest that the driving force for venous return is the pressure difference that remains within the venous system after the energy coming from every ventricular systole spent to overcome the resistance created by arterial and capillary systems.
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http://dx.doi.org/10.34172/bi.2021.13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022231PMC
March 2021

3D Bioprinted Bacteriostatic Hyperelastic Bone Scaffold for Damage-Specific Bone Regeneration.

Polymers (Basel) 2021 Mar 30;13(7). Epub 2021 Mar 30.

Department of Biomedical Engineering, Georgia Institute of Technology, School of Medicine, Emory University, Atlanta, GA 30322, USA.

Current strategies for regeneration of large bone fractures yield limited clinical success mainly due to poor integration and healing. Multidisciplinary approaches in design and development of functional tissue engineered scaffolds are required to overcome these translational challenges. Here, a new generation of hyperelastic bone (HB) implants, loaded with superparamagnetic iron oxide nanoparticles (SPIONs), are 3D bioprinted and their regenerative effect on large non-healing bone fractures is studied. Scaffolds are bioprinted with the geometry that closely correspond to that of the bone defect, using an osteoconductive, highly elastic, surgically friendly bioink mainly composed of hydroxyapatite. Incorporation of SPIONs into HB bioink results in enhanced bacteriostatic properties of bone grafts while exhibiting no cytotoxicity. In vitro culture of mouse embryonic cells and human osteoblast-like cells remain viable and functional up to 14 days on printed HB scaffolds. Implantation of damage-specific bioprinted constructs into a rat model of femoral bone defect demonstrates significant regenerative effect over the 2-week time course. While no infection, immune rejection, or fibrotic encapsulation is observed, HB grafts show rapid integration with host tissue, ossification, and growth of new bone. These results suggest a great translational potential for 3D bioprinted HB scaffolds, laden with functional nanoparticles, for hard tissue engineering applications.
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http://dx.doi.org/10.3390/polym13071099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036866PMC
March 2021

Can the biomolecular corona induce an allergic reaction?-A proof-of-concept study.

Biointerphases 2021 Feb 3;16(1):011008. Epub 2021 Feb 3.

Department of Radiology, Pediatric Molecular Imaging, Molecular Imaging Program at Stanford, Stanford University, Stanford, California 94305.

Ferumoxytol nanoparticles are being used clinically for the treatment of anemia and molecular imaging in patients. It is well documented that while most patients tolerate ferumoxytol well, a small percentage of patients (i.e., 0.01%) develop severe allergic reactions. The purpose of our proof-of-concept study was to determine whether patients with or without hypersensitivity reactions have specific protein corona profiles around ferumoxytol nanoparticles. In a retrospective, institutional review board approved pilot study, we enrolled 13 pediatric patients (5 girls, 8 boys, mean age 16.9 ± 8.2 years) who received a ferumoxytol-enhanced magnetic resonance imaging and who did (group 1, n = 5) or did not (group 2, n = 8) develop an allergic reaction. Blood samples of these patients were incubated with ferumoxytol, and the formation of a hard protein corona around ferumoxytol nanoparticles was measured by dynamic light scattering, zeta potential, and liquid chromatography-mass spectrometry. We also performed in vitro immune response analyses to randomly selected coronas from each group. Our results provide preliminary evidence that ex vivo analysis of the biomolecular corona may provide useful and predictive information on the possibility of severe allergic reactions to ferumoxytol nanoparticles. In the future, patients with predisposition of an allergic reaction to ferumoxytol may be diagnosed based on the proteomic patterns of the corona around ferumoxytol in their blood sample.
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http://dx.doi.org/10.1116/6.0000755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861880PMC
February 2021

The File Drawer Problem in Nanomedicine.

Trends Biotechnol 2021 May 8;39(5):425-427. Epub 2021 Feb 8.

Department of Radiology and Precision Health Program, Michigan State University, East Lansing, MI, USA. Electronic address:

The role of the 'file drawer' problem in nanomedicine, which partly drives the current limited clinical success of therapeutic nanoparticles, has been poorly investigated. We propose an integrated functioning of all stakeholders as the only effective way to address the file drawer problem in an efficient and timely manner.
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http://dx.doi.org/10.1016/j.tibtech.2021.01.009DOI Listing
May 2021

A missing, but essential, platform for multidisciplinary scientific discussion: understanding the 'elephant'.

Authors:
Morteza Mahmoudi

Future Sci OA 2020 Nov 30;7(3):FSO666. Epub 2020 Nov 30.

Department of Radiology & Precision Health Program, Michigan State University, East Lansing, MI 48824, USA.

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http://dx.doi.org/10.2144/fsoa-2020-0188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849986PMC
November 2020

Nanoscale characterization of the biomolecular corona by cryo-electron microscopy, cryo-electron tomography, and image simulation.

Nat Commun 2021 01 25;12(1):573. Epub 2021 Jan 25.

Department of Radiology and Precision Health Program, College of Human Medicine, Michigan State University, East Lansing, MI, USA.

The biological identity of nanoparticles (NPs) is established by their interactions with a wide range of biomolecules around their surfaces after exposure to biological media. Understanding the true nature of the biomolecular corona (BC) in its native state is, therefore, essential for its safe and efficient application in clinical settings. The fundamental challenge is to visualize the biomolecules within the corona and their relationship/association to the surface of the NPs. Using a synergistic application of cryo-electron microscopy, cryo-electron tomography, and three-dimensional reconstruction, we revealed the unique morphological details of the biomolecules and their distribution/association with the surface of polystyrene NPs at a nanoscale resolution. The analysis of the BC at a single NP level and its variability among NPs in the same sample, and the discovery of the presence of nonspecific biomolecules in plasma residues, enable more precise characterization of NPs, improving predictions of their safety and efficacies.
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http://dx.doi.org/10.1038/s41467-020-20884-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835367PMC
January 2021

Gender parity among the Altmetric Top 100 publications on COVID-19.

Authors:
Morteza Mahmoudi

Future Sci OA 2020 Nov 2;7(2):FSO651. Epub 2020 Nov 2.

Department of Radiology & Precision Health Program, Michigan State University, East Lansing, MI 48824, USA.

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http://dx.doi.org/10.2144/fsoa-2020-0175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643633PMC
November 2020

Synergistic Analysis of Protein Corona and Haemoglobin Levels Detects Pancreatic Cancer.

Cancers (Basel) 2020 Dec 30;13(1). Epub 2020 Dec 30.

Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 291, 00161 Rome, Italy.

Simultaneous detection of multiple analytes from a single biological sample is gaining more attention in the development of more reliable and point-of-care diagnostic devices. We developed a multiplexed strategy that combined outcomes of clinical biomarkers with analysis of the protein corona that forms around graphene oxide sheets upon exposure to patient's plasma. As a paradigmatic case study, we selected pancreatic ductal adenocarcinoma (PDAC), mainly because of the absence of effective detection strategies that resulted in an extremely low five-year survival rate after diagnosis (<10%). Association of protein corona analysis and haemoglobin levels discriminated PDAC patients from healthy volunteers in up to 90% of cases. If further confirmed in larger-cohort studies, this approach may be used in the detection of PDAC.
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http://dx.doi.org/10.3390/cancers13010093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796289PMC
December 2020

Filling the Space: A Framework for Coordinated Global Actions To Diminish Academic Bullying.

Angew Chem Int Ed Engl 2021 02 9;60(7):3338-3344. Epub 2020 Dec 9.

Department of Communication, Wayne State University, MI, USA.

Academic bullying is a serious issue that affects all disciplines and people of all levels of experience. To create a truly safe, productive, and vibrant environment in academia requires coordinated and collaborative input as well as the action of a variety of stakeholders, including scholarly communities, funding agencies, and institutions. In this Viewpoint, we focus on a framework of integrated responding, in which stakeholders as responsible and response-able parties could proactively collaborate and coordinate to reduce the incidence and consequences of academic bullying while at the same time building constructive academic cultures. The outcome of such a framework would be to create novel entities (e.g. centre of excellence in academic ethics and civility) and actions (e.g. incorporating bullying records into institutional rankings) that accelerate successful responses to academic bullying.
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http://dx.doi.org/10.1002/anie.202009270DOI Listing
February 2021

Implications of Biomolecular Corona for Molecular Imaging.

Mol Imaging Biol 2021 02 23;23(1):1-10. Epub 2020 Oct 23.

Precision Health Program, Michigan State University, East Lansing, MI, 48823, USA.

The development of nanoparticle probes has opened up new possibilities for molecular imaging in the era of precision medicine. There are a wide range of nanoprobes that are being used for various modalities that have demonstrated promising potential in early detection, disease monitoring, and theranostics. However, the rate of successful clinical translation of the nanoprobes is very low and is affected by the lack of our understanding about nanoparticle interaction with biological fluids after systemic administration, thus representing an unmet clinical need. One of the poorly understood issues relates to the formation of biomolecular corona, a layer of biomolecules formed on the surface of nanoscale materials during their interactions with biological fluids. The biomolecular corona has several significant effects on the biodistribution of nanoprobes and their imaging ability by (i) reducing their targeting efficacy and (ii) affecting the intrinsic imaging properties (e.g., contrast capacity of magnetic nanoprobes). This review provides insights on the importance of considering biomolecular corona in the development of nanoprobes, which may enable their more efficient utilization for molecular imaging applications.
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http://dx.doi.org/10.1007/s11307-020-01559-9DOI Listing
February 2021

A Healthier Peer Review Process Would Improve Diversity.

Authors:
Morteza Mahmoudi

ACS Appl Mater Interfaces 2020 09 1;12(37):40987-40989. Epub 2020 Sep 1.

Department of Radiology and Precision Health Program, Michigan State University, East Lansing, Michigan 48824, United States.

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http://dx.doi.org/10.1021/acsami.0c11528DOI Listing
September 2020

A survivor's guide to academic bullying.

Authors:
Morteza Mahmoudi

Nat Hum Behav 2020 11;4(11):1091

Department of Radiology and Precision Health Program, Michigan State University, Michigan, MI, USA.

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http://dx.doi.org/10.1038/s41562-020-00937-1DOI Listing
November 2020

Magnetic Levitation Systems for Disease Diagnostics.

Trends Biotechnol 2021 Mar 27;39(3):311-321. Epub 2020 Aug 27.

Department of Radiology and Precision Health Program, Michigan State University, East Lansing, MI, USA. Electronic address:

Magnetic levitation (MagLev) is a well-documented, robust technique for density measurements and separations. Although the potential of MagLev as an emerging tool in biotechnology has been recently investigated, the practical use of MagLev in diagnosis and disease detection merits further attention. This review highlights the diagnostic capacity of a simple and portable MagLev system and the possibilities and limitations of the MagLev technique for density-based separation, classification, and manipulation of soft matter and biological systems (e.g., cells, proteins), which in turn may pave the way for the discovery of disease-specific biomarkers.
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http://dx.doi.org/10.1016/j.tibtech.2020.07.010DOI Listing
March 2021

COVID-19 pandemic may fuel academic bullying.

Bioimpacts 2020 27;10(3):139-140. Epub 2020 Jun 27.

Department of Communication, Wayne State University, MI, USA.

The COVID-19 pandemic may exacerbate factors influencing abusive workplace behaviors in general such as psychological health, economic and social inequities. This is true in academic and research environments where we can expect to see an increase in the incidence of academic bullying. Research and experience shows that academic bullying will have significant and enduring negative effects on scientific integrity and academic health. In this perspective piece we will explore the potential facilitative influence of COVID-19 and specifically responses to it, on bullying behaviors in academic and research environments.
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http://dx.doi.org/10.34172/bi.2020.17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416009PMC
June 2020

COVID-19: Nanomedicine Uncovers Blood-Clot Mystery.

J Proteome Res 2020 11 31;19(11):4364-4373. Epub 2020 Aug 31.

Precision Health Program and Department of Radiology, Michigan State University, East Lansing, Michigan 48824, United States.

Further complications associated with infection by severe acute respiratory syndrome coronavirus 2 (a.k.a. SARS-CoV-2) continue to be reported. Very recent findings reveal that 20-30% of patients at high risk of mortality from COVID-19 infection experience blood clotting that leads to stroke and sudden death. Timely assessment of the severity of blood clotting will be of enormous help to clinicians in determining the right blood-thinning medications to prevent stroke or other life-threatening consequences. Therefore, rapid identification of blood-clotting-related proteins in the plasma of COVID-19 patients would save many lives. Several nanotechnology-based approaches are being developed to diagnose patients at high risk of death due to complications from COVID-19 infections, including blood clots. This Perspective outlines (i) the significant potential of nanomedicine in assessing the risk of blood clotting and its severity in SARS-CoV-2 infected patients and (ii) its synergistic roles with advanced mass-spectrometry-based proteomics approaches in identifying the important protein patterns that are involved in the occurrence and progression of this disease. The combination of such powerful tools might help us understand the clotting phenomenon and pave the way for development of new diagnostics and therapeutics in the fight against COVID-19.
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http://dx.doi.org/10.1021/acs.jproteome.0c00425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640964PMC
November 2020

A protein corona sensor array detects breast and prostate cancers.

Nanoscale 2020 Aug;12(32):16697-16704

Department of Molecular Medicine, "Sapienza" University of Rome, Viale Regina Elena 291, 00161 Rome, Italy.

Following exposure to human plasma (HP), nanoparticles (NPs) are coated with a biomolecular layer referred to as a protein corona. We recently revealed that characterizing the protein coronas of various NPs may provide a unique opportunity for cancer identification and discrimination. In other words, protein corona profiles of several NPs, when being analyzed using classifiers, would provide a unique "fingerprint" for each type of disease. Here, we probed the capacity of the protein corona for the identification and discrimination of breast and prostate cancer patients from healthy individuals. Using three lipid NP formulations with distinct physical-chemical properties as a cross-reactive sensor array and a supervised random forest classifier, we identified a set of proteins that showed a significant difference in cancer patients and control subjects. Our data show that many of the corona proteins with the highest discrimination ability between oncological patients and healthy individuals are related to cellular and molecular aspects of breast and prostate cancers.
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http://dx.doi.org/10.1039/d0nr03439hDOI Listing
August 2020

Biomolecular Corona Affects Controlled Release of Drug Payloads from Nanocarriers.

Trends Pharmacol Sci 2020 09 23;41(9):641-652. Epub 2020 Jul 23.

Department of Radiology and Precision Health Program, Michigan State University, East Lansing, MI, USA. Electronic address:

Nanomedicine has been widely used for a wide range of biomedical applications including drug delivery. Although many factors including the physicochemical properties of nanoparticles (NPs) and the payload efficacy of nanocarriers have been thoroughly investigated, the crucial role of the biomolecular corona in drug delivery and the release efficacy of nanocarriers demands further attention. This review highlights not only the crucial importance of the biomolecular corona to the drug release capacity of various types of nanocarriers, but also its interference with drug release measurements. A full consideration of the effects of the biomolecular corona on the controlled release and drug delivery of nanocarriers will help researchers design safer and more efficient nanobased drug delivery systems.
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http://dx.doi.org/10.1016/j.tips.2020.06.011DOI Listing
September 2020

Stretch Induces Invasive Phenotypes in Breast Cells Due to Activation of Aerobic-Glycolysis-Related Pathways.

Adv Biosyst 2019 07 7;3(7):e1800294. Epub 2019 May 7.

Nano Bio Electronic Devices Lab, School of Electrical and Computer Engineering, University of Tehran, P.O. Box 14395/515, Tehran, Iran.

It is increasingly being accepted that cells' physiological functions are substantially dependent on the mechanical characteristics of their surrounding tissue. This is mainly due to the key role of biomechanical forces on cells and their nucleus' shapes, which have the capacity to regulate chromatin conformation and thus gene regulations. Therefore, it is reasonable to postulate that altering the biomechanical properties of tissue may have the capacity to change cell functions. Here, the role of cell stretching (as a model of biomechanical variations) is probed in cell migration and invasion capacity using human normal and cancerous breast cells. By several analyses (i.e., scratch assay, invasion to endothelial barrier, real-time RNA sequencing, confocal imaging, patch clamp, etc.), it is revealed that the cell-stretching process could increase the migration and invasion capabilities of normal and cancerous cells, respectively. More specifically, it is found that poststretched breast cancer cells are found in low grades of invasion; they substantially upregulate the expression of manganese-dependent superoxide dismutase (MnSOD) through activation of H-Ras proteins, which subsequently induce aerobic glycolysis followed by an overproduction of matrix metalloproteinases (MMP)-reinforced filopodias. Presence of such invadopodias facilitates targeting of the endothelial layer, and increased invasive behaviors in breast cells are observed.
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http://dx.doi.org/10.1002/adbi.201800294DOI Listing
July 2019

Effect of cell imprinting on viability and drug susceptibility of breast cancer cells to doxorubicin.

Acta Biomater 2020 09 7;113:119-129. Epub 2020 Jun 7.

Departments of Bioengineering, Chemical and Biomolecular Engineering and Radiological Sciences, Center for Minimally Invasive Therapeutics, California NanoSystems Institute, University of California - Los Angeles, Los Angeles, CA, USA; Terasaki Institute for Biomedical Innovation, Los Angeles, CA, USA. Electronic address:

This study demonstrates the effect of substrate's geometrical cues on viability and the efficacy of an anti-cancer drug, doxorubicin (DOX), on breast cancer cells. It is hypothesized that the surface topographical properties can mediate the cellular drug intake. Pseudo-three dimensional (3D) platforms were fabricated using imprinting technique from polydimethylsiloxane (PDMS) and gelatin methacryloyl (GelMA) hydrogel to recapitulate topography of cells' membranes. The cells exhibited higher viability on the cell-imprinted platforms for both PDMS and GelMA materials compared to the plain/flat counterparts. For instance, MCF7 cells showed a higher metabolic activity (11.9%) on MCF7-imprinted PDMS substrate than plain PDMS. The increased metabolic activity for the imprinted GelMA was about 44.2% compared to plain hydrogel. The DOX response of cells was monitored for 24 h. Although imprinted substrates demonstrated enhanced biocompatibility, the cultured cells were more susceptible to the drug compared to the plain substrates. In particular, MCF7 cells on imprinted PDMS and GelMA substrates showed 37% and 50% higher in cell death compared to the corresponding plain PDMS and GelMA, respectively. Interestingly, the drug susceptibility of the cells on the imprinted hydrogel was about 70% higher than the cells cultured on imprinted PDMS substrates. Having MCF7 cell-imprinted substrates, DOX responses of two other breast cancer cell lines, SKBR3 and ZR-75-1, were also evaluated. The results support that cell membrane curvature developed by multiscale topography is able to mediate intracellular signaling and drug intake. STATEMENT OF SIGNIFICANCE: Research in biological sciences and drug discovery mostly rely on two dimensional (2D) cell culture techniques which cannot provide a reliable physiologically relevant environment. Lack of extracellular matrix and a large shift in physicochemical properties of conventional 2D substrates can induce aberrant cellular behaviors. While chemical composition, topographical, and mechanical properties of substrates have remarkable impacts on drug susceptibility, gene expression, and protein synthesis, the most cell culture plates are from rigid and plain substrates. A number of (bio)polymeric 3D-platforms have been introduced to resemble innate cell microenvironment. However, their intricate culture protocols restrain their applications in demanding high-throughput drug screening. To address the above concerns, in the present study, a hydrogel-based pseudo-3D substrate with imprinted cell features has been introduced.
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http://dx.doi.org/10.1016/j.actbio.2020.06.007DOI Listing
September 2020

Nanomedicine in Healing Chronic Wounds: Opportunities and Challenges.

Mol Pharm 2021 02 10;18(2):550-575. Epub 2020 Jun 10.

Department of Radiology and Precision Health Program, Michigan State University, East Lansing, Michigan 48824, United States.

The poor healing associated with chronic wounds affects millions of people worldwide through high mortality rates and associated costs. Chronic wounds present three main problems: First, the absence of a suitable environment to facilitate cell migration, proliferation, and angiogenesis; second, bacterial infection; and third, unbalanced and prolonged inflammation. Unfortunately, current therapeutic approaches have not been able to overcome these main issues and, therefore, have limited clinical success. Over the past decade, incorporating the unique advantages of nanomedicine into wound healing approaches has yielded promising outcomes. Nanomedicine is capable of stimulating various cellular and molecular mechanisms involved in the wound microenvironment via antibacterial, anti-inflammatory, and angiogenetic effects, potentially reversing the wound microenvironment from nonhealing to healing. This review briefly discusses wound healing mechanisms and pathophysiology and then highlights recent findings regarding the opportunities and challenges of using nanomedicine in chronic wound management.
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http://dx.doi.org/10.1021/acs.molpharmaceut.0c00346DOI Listing
February 2021

Emerging Biomolecular Testing to Assess the Risk of Mortality from COVID-19 Infection.

Authors:
Morteza Mahmoudi

Mol Pharm 2021 02 20;18(2):476-482. Epub 2020 May 20.

Precision Health Program and Department of Radiology, Michigan State University, East Lansing, Michigan 48824, United States.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 and COVID-19) has produced an unprecedented global pandemic. Though the death rate from COVID-19 infection is ∼2%, many infected people recover at home. Among patients for whom COVID-19 is deadly are those with pre-existing comorbidities. Therefore, identification of populations at highest risk of COVID-19 mortality could significantly improve the capacity of healthcare providers to take early action and minimize the possibility of overwhelming care centers, which in turn would save many lives. Although several approaches have been used/developed (or are being developed/suggested) to diagnose COVID-19 infection, no approach is available/proposed for fast diagnosis of COVID-19 infections likely to be fatal. The central aim of this short perspective is to suggest a few possible nanobased technologies (i.e., protein corona sensor array and magnetic levitation) that could discriminate COVID-19-infected people while still in the early stages of infection who are at high risk of death. Such discrimination technologies would not only be useful in protecting health care centers from becoming overwhelmed but would also provide a powerful tool to better control possible future pandemics with a less social and economic burden.
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http://dx.doi.org/10.1021/acs.molpharmaceut.0c00371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241738PMC
February 2021

The absence of legal remedies following academic bullying.

Bioimpacts 2020 28;10(2):63-64. Epub 2019 Nov 28.

School of Business, Wake Forest University, NC, USA.

Currently, victims of discrimination and sexual harassment have institutional reporting systems and legal remedies which support them in finding justice for these crimes. However, victims of academic bullying, who suffer similar repercussions, have no legal or institutional remedies. Because academic bullying is not a crime, targets often suffer in silence because there is no recourse. It is time for institutions to ask for governmental support to create legislation, similar to that for sexual harassment and discrimination, which will bring justice to academic bullies and relief to their victims. In the absence of legislation, institutions should create reporting procedures and educational programs which mirror those they have in place for sexual harassment and discrimination.
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http://dx.doi.org/10.34172/bi.2020.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186547PMC
November 2019