New technology to monitor chemotherapy using magnetic nanoparticles

Researchers from Michigan State University propose a novel non-invasive magnetic particle imaging (MPI) to monitor chemotherapy release in vivo. This method employs superparamagnetic nanoparticles as the contrast agent to monitor drug release in the body.

In this study researchers designed iron oxide nanocomposite loaded with a chemotherapy drug doxorubicin which serves as a drug delivery system and magnetic particle imaging (MPI) quantification tracer. They showed that nanocomposite-induced MPI signal changes display a linear correlation with the release rate of doxorubicin over time.

Researchers performed this study in both in-vitro cell cultures and murine breast cancer model.

Implications: In vivo drug monitoring technologies are important as they monitor adequate drug release at the site of tumors. Being non-invasive as it is easier to perform and repeat.

This research is published Nano Letters (ACS publications)

Understanding interaction between heart muscle cells and nanoscaffoding

Researchers from Moscow Institute of Physics and Technology (MIPT) have researched nanofibrous scaffold structure and its interaction with rat heart muscle cells.  This study revealed that cardiac muscle cells envelop nanofibers as they grow, but fibroblasts tend to spread out on fibers forming several focal adhesion sites.

Nanofibers enveloped by Heart muscle cells. The 3-D model was reconstructed using scanning probe nanotomography.
Credit: Moscow Institute of Physics and Technology.

The study was conducted at MIPT’s Laboratory of Biophysics of Excitable Systems in collaboration with the researchers from the Shumakov Federal Research Center of Transplantology and Artificial Organs and the Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences. The article is published in the journal Acta Biomaterialia.

“Using three independent methods, we discovered that during their development on a nanofibrous scaffold, cardiomyocytes wrap the fibers on all sides creating a ‘sheath’ structure in the majority of cases,” explains Professor Konstantin Agladze, head of the Laboratory of Biophysics of Excitable Systems. “Fibroblasts, by contrast, have a more rigid structure and a much smaller area of interaction with the substrate, touching it only on one side.”

The scaffolds used for cardiac tissue engineering are based on a matrix of polymer nanofibers. Nanofibers may vary regarding elasticity and electrical conductivity, or they may have additional “smart” functions allowing them to release biologically active molecules at a certain stage. Nanofibers are designed to mimic the extracellular matrix, which surrounds the cells, providing structural support. Also, nanofibers can be used as a medium for delivering substances into the surrounding cells to induce biochemical changes in them.

The team conducted a three-stage study. First, the researchers examined the structure of cardiomyocytes (heart muscle cells) and fibroblasts (connective tissue cells) grown on a substrate of nanofibers using confocal laser scanning microscopy. Cell samples were then sectioned into ultrathin slices in a plane perpendicular to the direction of the fibers and “photographed” using transmission electron microscopy (TEM). The researchers discovered that heart muscle cells envelop nanofibers on all sides so that the fiber ends up being in the middle of the cell. Nevertheless, it remains separated from the cytoplasm by the cell membrane.

Connective tissue cells, on the other hand, do not “swallow” the fiber; they only touch it on one side. Moreover, transmission electron microscopy images demonstrate that the nucleus of the fibroblast is relatively rigid compared to other cell components. This makes fibroblasts less flexible, reducing their ability to stretch along the fiber. Transmission electron microscopy made it possible to study the cross sections. Then, using scanning probe nanotomography, a comprehensive 3-D model was created.

Researchers observed some crucial aspects of the cell-fiber interaction. First of all, since stronger mechanical adhesion, i.e., the cell-scaffold attachment means cells are more stable growing on the substrate, heart muscle cells will be firmly attached to the scaffold, while fibroblasts will be less stable.

Secondly, additional “smart” scaffold functions, such as the release of growth factors will also differ depending on the cell type. In the case of heart muscle cells, which tend to envelop the nanofiber, the released substances will diffuse directly from the fiber through the cell membrane and into the cytoplasm. In the case of fibroblasts, on the other hand, a certain amount of these substances will leak out.

Thirdly, heart muscle cells isolate the polymer fibers from the surrounding solution. Since heart muscle cells are responsible for the transfer of electromagnetic waves within the heart immersing the fibers of the scaffold entirely in heart muscle cells will enable researchers to test the electrical conductivity of the cells.

Researchers feel that this study will enable the creation of nanofibers that would provide cells with the properties needed to form regenerative tissues.

Citation: Balashov, Victor, Anton Efimov, Olga Agapova, Alexander Pogorelov, Igor Agapov, and Konstantin Agladze. “High resolution 3D microscopy study of cardiomyocytes on polymer scaffold nanofibers reveals formation of unusual sheathed structure.” Acta Biomaterialia 68 (2018): 214-22. doi:10.1016/j.actbio.2017.12.031.

Research funding: Ministry of Education and Science of the Russian Federation

Adapted from press release by Moscow Institute of Physics and Technology  (MIPT)

Researchers create better wearable medical sensors based on graphene nano-flakes

Team of researchers at University of British Columbia Okanagan campus have developed a practical way to monitor and interpret human motion.The sensor is made by infusing graphene nano-flakes (GNF) into a rubber-like adhesive pad. Najjaran says they then tested the durability of the tiny sensor by stretching it to see if it can maintain accuracy under strains of up to 350 per cent of its original state. The device went through more than 10,000 cycles of stretching and relaxing while maintaining its electrical stability.

“We tested this sensor vigorously,” says Najjaran. “Not only did it maintain its form but more importantly it retained its sensory functionality. We have further demonstrated the efficacy of GNF-Pad as a haptic technology in real-time applications by precisely replicating the human finger gestures using a three-joint robotic finger.”

The goal was to make something that could stretch, be flexible and a reasonable size, and have the required sensitivity, performance, production cost, and robustness. Unlike an inertial measurement unit (an electronic unit that measures force and movement and is used in most step-based wearable technologies) Najjaran says the sensors need to be sensitive enough to respond to different and complex body motions. That includes infinitesimal movements like a heartbeat or a twitch of a finger, to large muscle movements from walking and running.

School of Engineering Professor and study co-author Mina Hoorfar says their results may help manufacturers create the next level of health monitoring and biomedical devices. “We have introduced an easy and highly repeatable fabrication method to create a highly sensitive sensor with outstanding mechanical and electrical properties at a very low cost,” says Hoorfar.

To demonstrate its practicality, researchers built three wearable devices including a knee band, a wristband and a glove. The wristband monitored heartbeats by sensing the pulse of the artery. In an entirely different range of motion, the finger and knee bands monitored finger gestures and larger scale muscle movements during walking, running, sitting down and standing up. The results, says Hoorfar, indicate an inexpensive device that has a high-level of sensitivity, selectivity and durability.

Citation: Larimi, Seyed Reza, Hojatollah Rezaei Nejad, Michael Oyatsi, Allen O’Brien, Mina Hoorfar, and Homayoun Najjaran. “Low-cost ultra-stretchable strain sensors for monitoring human motion and bio-signals.” Sensors and Actuators A: Physical 271 (2018): 182-91. doi:10.1016/j.sna.2018.01.028.

Research funding: Natural Sciences and Engineering Research Council.

Adapted from press release by the University of British Columbia.

New nanofiber bandages accelerate healing process

Researchers from National University of Science and Technology MSIS has presented a new therapeutic material based on nanofibers made of polycaprolactone modified with a thin-film antibacterial composition and plasma components of human blood. Biodegradable bandages made from these fibers will accelerate the growth of tissue cells twice as quickly, contributing to the normal regeneration of damaged tissues, as well as preventing the formation of scars in cases of severe burns.

New therapeutic material based on nanofibers made of polycaprolactone. Credit: NUST MSIS

In regenerative medicine, and particularly in burn therapy, the effective regeneration of damaged skin tissue and the prevention of scarring are usually the main goals. Scars form when skin is badly damaged, whether through a cut, burn, or a skin problem such as acne or fungal infection.

Scar tissue mainly consists of irreversible collagen and significantly differs from the tissue it replaces, having reduced functional properties. For example, scars on skin are more sensitive to ultraviolet radiation, are not elastic, and the sweat glands and hair follicles are not restored in the area.

The solution of this medical problem was proposed by the researchers from Inorganic Nanomaterials Laboratory, led by PhD Anton Manakhov, a senior researcher. The team of scientists has managed to create multi-layer bandages made of biodegradable fibers and multifunctional bioactive nanofilms, which prevent scarring and accelerate tissue regeneration.

The addition of the antibacterial effect by the introduction of silver nanoparticles or joining antibiotics, as well as the increase of biological activity to the surface of hydrophilic groups and the blood plasma proteins have provided unique healing properties to the material.

A significant acceleration of the healing process, the successful regeneration of normal skin covering tissue, and the prevention of scarring on the site of burnt or damaged skin have been observed when applying these bandages made of the developed material to an injured area. The antibacterial components of multifunctional nanofibers decrease inflammation, and the blood plasma with an increased platelet level vital and multi-purposed for every element in the healing process stimulates the regeneration of tissues. The bandages should not be removed or changed during treatment as it may cause additional pain to the patient. After a certain period of time, the biodegradable fiber simply «dissolves» without any side effects.

“With the help of chemical bonds, we were able to create a stable layer containing blood plasma components (growth factors, fibrinogens, and other important proteins that promote cell growth) on a polycaprolactone base. The base fibers were synthesized by electroforming. Then, with the help of plasma treatment, to increase the material`s hydrophilic properties, a polymer layer containing carboxyl groups was applied to the surface. The resulting layer was enriched with antibacterial and protein components.” noted Elizabeth Permyakova, one of the project members and laboratory scientists.

The research team has already conducted a series of pre-clinical trials jointly with the Research Institute of Experimental and Clinical Medicine (Novosibirsk, Russia). In vitro results have shown that with the application of these innovative bandages the regeneration process has been accelerated twice as quickly. In the near future, the team expects to get results of in vivo drug testing.

Adapted from press release by National University of Science and Technology MSIS.

Gene therapy using lipid based nanoparticles

Lipid nanoparticles (SLNs and NLCs) are regarded as highly promising systems for delivering nucleic acids in gene therapy. Literature review by researchers at PharmaNanoGene describes these systems and their main advantages in gene therapy, such as their capacity to protect the gene material against degradation, to facilitate cell and nucleus internalization and to boost the transfection process.


View of lipid nanoparticles.
View of lipid nanoparticles. Credit: UPV/EHU

“At PharmaNanoGene we are working on the design and evaluation of SLNs for treating some of these diseases using gene therapy. We are studying the relationship between formulation factors and the processes involving the intracellular internalisation and disposition of the genetic material that condition the effectiveness of the vectors and which is essential in the optimisation process, and for the first time we have demonstrated the capacity of SLNs to induce the synthesis of a protein following their intravenous administration in mice,” they stressed.

The publication also includes other pieces of work by this University of the Basque Country research group on the application of SLNs in the treatment of rare diseases, such as chromosome-X-linked juvenile retinoschisis, a disorder in which the retina becomes destructured due to a deficiency in the protein retinoschisin.

 “One of the main achievements of our studies in this field has been to demonstrate, also for the first time, the capacity of a non-viral vector to transfect the retina of animals lacking the gene that encodes this protein and partially restore its structure, showing than non-viral gene therapy is a viable, promising therapeutic tool for treating degenerative disorders of the retina,” specified the researchers.
The application of SLNs for treating Fabry disease, a serious, multi-system metabolic disorder of a hereditary nature, has also been studied at PharmaNanoGene.

 “This is a monogenic disease linked to the X-chromosome which is caused by various gene mutations in the gene that encodes the galactosidase A enzyme. In cell models of this disease we have demonstrated the capacity of SLNs to induce the synthesis of galactosidase A enzyme”. They have also reviewed the application of lipid nanoparticles to the treatment of infectious diseases: “Our work in this field shows that SLNs with RNA interference are capable of inhibiting a replicon of the hepatitis C virus in vitro, which was used as proof-of-concept of the use of SLN-based vectors as a new therapeutic strategy for treating this infection and others related to it”.

Citation: Ana del Pozo-Rodríguez, María Ángeles Solinís, Alicia Rodríguez-Gascón, Applications of lipid nanoparticles in gene therapy, European Journal of Pharmaceutics and Biopharmaceutics, Volume 109, December 2016, Pages 184-193.
DOI: 10.1016/j.ejpb.2016.10.016.
Adapted from press release by University of the Basque Country.

Development of thin-film biomaterials using nanofibres to be used as scaffolding for bone regeneration

In future, it may be possible to use nanofibres to improve the attachment of bone implants, or the fibres may be used directly to scaffold bone regeneration. This would aid the healing of fractures and may enable the care of osteoporosis. This is detailed in a new dissertation.

Hydroxyapatite nanofibre film produced at the University of Helsinki Credit: Riitta-Leena Inki

In his doctoral research, Jani Holopainen of the Department of Chemistry at the University of Helsinki has developed processes for fibrous and thin-film biomaterials that can be used as scaffolding for bone regeneration and in other bone implants. He also studied the apparatus used for nanofibre production.

At best, bone-reforming scaffolds that regenerate at the same rate as bones could be used as implants. The scaffolds activate the bone cells to generate new bone that slowly replaces the disintegrating scaffold and the implant exits the body naturally without separate removal surgery, Jani Holopainen says.

Holopainen selected hydroxyapatite, the main component of the bone mineral, as the focus of his research. This is why the synthetic hydroxyapatite structures he has developed are very compatible with bone.

Holopainen developed the electrospinning apparatus for producing hydroxyapatite fibres and a new kind of needle less twisted wire electrospinning setup, which is more productive than the generally known electrospinning method. The prototypes for the equipment used in the research were manufactured at the Department of Chemistry at the University of Helsinki. The equipment will have to be developed further in order to enhance production to an industrial scale.

This promising method still has a long way to go before it will become a real medical application, though cellular tests have already been made, says Professor Mikko Ritala of the Department of Chemistry and the Atomic Layer Deposition centre of excellence at the University of Helsinki, who was the adviser of the doctoral research.

Citation: Holopainen, Jani. “Bioactive Coatings and Fibers for Bone Implants and Scaffolds by Atomic Layer Deposition, Electrospinning, Solution Blow Spinning and Electroblowing.”Doctoral dissertation, University of Helsinki (2017).
URN:ISBN:978-951-51-2672-6 
hdl.handle.net/10138/169566
Adapted from press release by University of Helsinki.

MESO-BRAIN stem cell research project to develop 3D nanoprinting techniques to replicate neural networks

Aston University heading up major €3.3m stem cell research project to develop 3D nanoprinting techniques that could replicate brain’s neural networks.

Aston University has launched MESO-BRAIN, a major stem cell research project which it hopes will develop three-dimensional (3D) nanoprinting techniques that can be used to replicate the brain’s neural networks.

The cornerstone of the MESO-BRAIN project will be its use of pluripotent stem cells generated from adult human cells that have been turned into brain cells, which will form neural networks with specific biological architectures. Advanced imaging and detection technologies developed in the project will be used to report on the activity of these networks in real time.

Credit: Ashton University
Such technology would mark a new era of medical and neuroscience research which would see screening and testing conducted using physiologically relevant 3D living human neural networks. In the future, this could potentially be used to generate networks capable of replacing damaged areas in the brains of those suffering from Parkinson’s disease, dementia or other brain trauma.
The MESO-BRAIN initiative, which will span three years, received €3.3million of funding from the European Commission as part of its prestigious Future and Emerging Technology (FET) scheme. Aston University is leading the project, with partners from industry and higher education across Europe: Axol Bioscience Ltd, Laser Zentrum Hannover, The Institute of Photonic Sciences, University of Barcelona and Kite Innovations. This unique partnership brings together stem cell biologists, neuroscientists, photonics experts and physicists.

Head of the MESO-BRAIN project, Professor Edik Rafailov, said: “What we’re hoping to achieve with this project has, until recently, been the stuff of science-fiction.

“If we can use 3D nanoprinting to improve the connection of neurons in an area of the brain which has been damaged, we will be in a position to develop much more effective ways to treat those with dementia or brain injuries.

“To date, attempts to replicate and reproduce cells in this way have only ever delivered 2D tissues or poorly defined 3D tissues that do not resemble structures found within the human body. The new form of printing we are aiming to develop promises to change this. The MESO-BRAIN project could improve hundreds of thousands of lives.”

Dr Eric Hill, Programme Director for MSc Stem cells and Regenerative Medicine at Aston University, commented: “This research carries the potential to enable us to recreate brain structures in a dish. This will allow us to understand how brain networks form during development and provide tools that will help us understand how these networks are affected in diseases such as Alzheimer’s disease.”

Adapted from press release by Ashton University.

New approach to treating cancer with therapeutic short interfering RNA (siRNA) delivered by nanohydrogel nanoparticles

A novel targeted therapy using nanoparticles has enabled researchers at the Georgia Institute of Technology to purge ovarian tumors in limited, in vivo tests in mice. “The dramatic effect we see is the massive reduction or complete eradication of the tumor, when the ‘nanohydrogel’ treatment is given in combination with existing chemotherapy,” said chief researcher John McDonald.

That nanohydrogel is a minute gel pellet that honed in on malignant cells with a payload of an RNA strand. The RNA entered the cell, where it knocked down a protein gone awry that is involved in many forms of cancer.

In trials on mice, it put the brakes on ovarian cancer growth and broke down resistance to chemotherapy. That allowed a common chemotherapy drug, cisplatin, to drastically reduce or eliminate large carcinomas with very similar speed and manner. The successful results in treatment of four mice with the combination of siRNA and cisplatin showed little variance.

The therapeutic short interfering RNA (siRNA) developed by McDonald and Georgia Tech researchers Minati Satpathy and Roman Mezencev, thwarted cancer-causing overproduction of cell structures called epidermal growth factor receptors (EGFRs), which extend out of the wall of certain cell types. EGFR overproduction is associated with aggressive cancers. The nanohydrogel that delivers the siRNA to the cancer cells is a colloid ball of a common, compact organic molecule and about 98 percent water. Another molecule is added to the surface of the nanohydrogel as a guide. In the in vivo trials, the siRNA, which contained a fluorescent tag, allowed researchers to observe nanoparticles successfully honing in on the cancer cells.

The researchers from Georgia Tech’s School of Biological Sciences published their results on Monday, November 7, 2016, in the journal Scientific Reports.

The new treatment has not been tested on humans, and research would be required by science and by law to demonstrate consistent results – efficacy – among other things, before preliminary human trials could become possible.

Citation: Minati Satpathy, Roman Mezencev, Lijuan Wang & John F. McDonald. “Targeted in vivo delivery of EGFR siRNA inhibits ovarian cancer growth and enhances drug sensitivity”
Scientific Reports 6, Article number: 36518 (2016)
DOI: http://dx.doi.org/10.1038/srep36518
Research funding: National Institutes of Health’s IMAT Program, Ovarian Cancer Institute, Deborah Nash Endowment Fund, Curci Foundation and Markel Foundation.
Adapted from press release by Georgia Institute of Technology

Nanomedicine: Nanotechnology and Nanoscience for better health

Nanoscience research involves molecules that are tiny compared to the size of cancer cells and that have the potential to profoundly improve the quality of our health and our lives. Now nine prominent Nano scientists look ahead to what we can expect in the coming decade, and conclude that nanoscience is poised to make important contributions in many areas, including health care, electronics, energy, food and water. The researchers discuss the need to safely implement new nanomaterials and present ideas for doing so. They also call for researchers to communicate their research with the public.

Paul Weiss (UC presidential chair and distinguished professor of chemistry and biochemistry at UCLA) and Dr. Andre Nel, (Chief of nanomedicine at the David Geffen School of Medicine at UCLA) who written a paper about Nanoscience and Nanotechnology in Journal ACS Nano, think that significant progress is already made. Some important points made by authors in the publication include the following with respect to medicine and health.

  • Nanoparticles can be designed to target infectious disease. Nanomaterials may target the lungs to deliver potent antibiotics and anti-inflammatory drugs could fight bacterial and viral infection.
  • Nanoparticles may lead to more effective treatments of neurological disorders such as Parkinson’s disease and Alzheimer’s disease, as well as arthritis.
  • The emerging field of immuno-oncology is likely to produce advances that will activate the body’s immune system to attack tumor cells. Important advantages of nanoparticles are that they can bind selectively to receptors over-expressed on tumors and may be delivered to the same cell at a predetermined dose and timing, although significant scientific challenges remain.
Illustration of ultra thin materials.
Credit: Patrick Han, ACS Nano

Authors also feel that Nanotechnology will be a major part of other aspects of day today life including following areas.
  • The microelectronics industry has been manufacturing products with nanoscale structures for decades — a market currently valued at approximately $500 billion annually. The researchers say there is still plenty of room for major improvements, including many opportunities in creative design of devices for data processing and information storage.
  • Nanotechnology is likely to capture, convert and store energy with greater efficiency, and will help to safely produce sustainable and efficient large-scale energy production to meet the increasing worldwide demand for energy.
  • Nanotechnology principles are being used in water desalination and purification, and nanotechnology is poised to make major contributions to supplying clean water globally.
  • Technology is likely to become increasingly widespread, with the proliferation of “nano-enabled smart devices” in such areas as telecommunications, consumer staples and information technology.
  • Nanoscience advances may lead to advances in food safety and reductions in food contamination. Sensor technologies may be designed that exploit changes at the surface of nanostructures so they can detect disease-causing pathogens before they spread. Nanoscale sensor technologies also may lead to improvements in agrochemicals.

The researchers advocate strong federal support for nanoscience, and predict significant progress toward major scientific goals will be achieved by the end of this decade. They also advocate basic research to produce currently unforeseen discoveries.

Citation: Nano Day: Celebrating the Next Decade of Nanoscience and Nanotechnology
Authors: Cherie R Kagan, et., al.
DOI: http://dx.doi.org/10.1021/acsnano.6b06655
Journal: ACS Nano
Adapted from press release by UCLA

Researchers focus on using Nanoparticles to improve drug delivery in HIV patients

New research led by the University of Liverpool aims to improve the administration and availability of drug therapies to HIV patients through the use of nanotechnology.  The research, conducted by the collaborative nanomedicine research programme led by Pharmacologist Professor Andrew Owen and Materials Chemist Professor Steve Rannard, examined the use of nanotechnology to improve the delivery of drugs to HIV patients.

Currently, the treatment of HIV requires daily oral dosing of HIV drugs, and chronic oral dosing has significant complications that arise from the high pill burden experienced by many patients across populations with varying conditions leading to non-adherence to therapies.

Recent evaluation of HIV patient groups have shown a willingness to switch to nanomedicine alternatives if benefits can be shown. Research efforts by the Liverpool team have focused on the development of new oral therapies, using Solid Drug Nanoparticle (SDN) technology which can improve drug absorption into the body, reducing both the dose and the cost per dose and enabling existing healthcare budgets to treat more patients.

Presently, no clinically available oral nanotherapies exist for HIV populations and conventional paediatric HIV medicines are poorly available. The programme examined one current paediatric formulation that utilizes high ethanol concentrations to solubilize lopinavir, a poorly soluble antiretroviral.

Through the use of a rapid small-scale nanomedicine screening approach developed at Liverpool, the researchers were able to generate a novel water dispersible nanotherapy, hence removing the need to use alcohol in the paediatric medicine.

The research, funded by the UK Engineering and Physical Sciences Research Council is in ongoing human trials, and the preclinical development has been published in Nature Communications today (Friday, 21 October 2016).

Publication: Accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric HIV nanotherapies.
DOI: http://dx.doi.org/10.1038/ncomms13184
Authors:Marco Giardiello et.al,
Journal: Nature Communications – News
Adapted from press release by University of Liverpool