Graphene microbubbles make perfect lenses – And Much More … Drug Delivery .. Water Treatment

In situ optical microscopic images showing the process of the microbubble generation and elimination. Credit: H. Lin et al

Tiny bubbles can solve large problems. Microbubbles—around 1-50 micrometers in diameter—have widespread applications. They’re used for drug delivery, membrane cleaning, biofilm control, and water treatment. They’ve been applied as actuators in lab-on-a-chip devices for microfluidic mixing, ink-jet printing, and logic circuitry, and in photonics lithography and optical resonators. And they’ve contributed remarkably to biomedical imaging and applications like DNA trapping and manipulation.

Given the broad range of applications for microbubbles, many methods for generating them have been developed, including air stream compression to dissolve air into liquid, ultrasound to induce bubbles in water, and laser pulses to expose substrates immersed in liquids. However, these bubbles tend to be randomly dispersed in liquid and rather unstable.

According to Baohua Jia, professor and founding director of the Centre for Translational Atomaterials at Swinburne University of Technology, “For applications requiring precise bubble position and size, as well as high stability—for example, in photonic applications like imaging and trapping—creation of bubbles at accurate positions with controllable volume, curvature, and stability is essential.” Jia explains that, for integration into biological or photonic platforms, it is highly desirable to have well controlled and stable microbubbles fabricated using a technique compatible with current processing technologies.

Balloons in graphene

Jia and fellow researchers from Swinburne University of Technology recently teamed up with researchers from National University of Singapore, Rutgers University, University of Melbourne, and Monash University, to develop a method to generate precisely controlled graphene microbubbles on a glass surface using laser pulses. Their report is published in the peer-reviewed, open-access journal, Advanced Photonics.

Photonic jet focused by a graphene oxide microbubble lens. Credit: H. Lin et al., doi 10.1117/1.AP.2.5.055001

The group used graphene oxide materials, which consist of graphene film decorated with oxygen functional groups. Gases cannot penetrate through graphene oxide materials, so the researchers used laser to locally irradiate the graphene oxide film to generate gases to be encapsulated inside the film to form microbubbles—like balloons. Han Lin, Senior Research Fellow at Swinburne University and first author on the paper, explains, “In this way, the positions of the microbubbles can be well controlled by the laser, and the microbubbles can be created and eliminated at will. In the meantime, the amount of gases can be controlled by the irradiating area and irradiating power. Therefore, high precision can be achieved.”

Such a high-quality bubble can be used for advanced optoelectronic and micromechanical devices with high precision requirements.

The researchers found that the high uniformity of the graphene oxide films creates microbubbles with a perfect spherical curvature that can be used as concave reflective lenses. As a showcase, they used the concave reflective lenses to focus light. The team reports that the lens presents a high-quality focal spot in a very good shape and can be used as light source for microscopic imaging.

Lin explains that the reflective lenses are also able to focus light at different wavelengths at the same focal point without chromatic aberration. The team demonstrates the focusing of a ultrabroadband white light, covering visible to near-infrared range, with the same high performance, which is particularly useful in compact microscopy and spectroscopy.

Jia remarks that the research provides “a pathway for generating highly controlled microbubbles at will and integration of graphene microbubbles as dynamic and high precision nanophotonic components for miniaturized lab-on-a-chip devices, along with broad potential applications in high resolution spectroscopy and medical imaging.”

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Monolayer transition metal dichalcogenide lens for high resolution imaging

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More information: Han Lin et al, Near-perfect microlenses based on graphene microbubbles, Advanced Photonics (2020). DOI: 10.1117/1.AP.2.5.055001

Provided by SPIE

Targeted drug delivery could help fight tumors and local infections

Some drug regimens, such as those designed to eliminate tumors, are notorious for nasty side effects. Unwanted symptoms are often the result of medicine going where it’s not needed and harming healthy cells. To minimize this risk, researchers in Quebec have developed nanoparticles that only release a drug when exposed to near-infrared light, which doctors could beam onto a specific site. Their report appears in the Journal of the American Chemical Society.

For years, scientists have been striving to develop localized treatments to reduce side effects of therapeutic drugs. They have designed drug-delivery systems that respond to light, temperature, ultrasound and pH changes. One promising approach involved drug-carrying materials that are sensitive to ultraviolet (UV) light. Shining a beam in this part of the light spectrum causes the materials to release their therapeutic cargo at a designated location. But UV light has major limitations. It can’t penetrate body tissues, and it is carcinogenic. Near-infrared (NIR) light can go through 1 to 2 centimeters of tissue and would be a safer alternative, but photosensitive drug-carriers don’t react to it. McGill University engineering professor Marta Cerruti and colleagues sought a way to bring the two kinds of light together in one possible solution.

The researchers started with nanoparticles that convert NIR light into UV light and coated them in a UV-sensitive hydrogel shell infused with a fluorescent protein, a stand-in for drug molecules. When exposed to NIR light, the nanoparticles instantaneously converted it to UV, which induced the shell to release the protein payload. The researchers note that their on-demand delivery system could not only supply drug molecules but also agents for imaging and diagnostics.

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The above post is reprinted from materials provided by McGill University. Note: Materials may be edited for content and length.

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Journal Reference:

1. Ghulam Jalani, Rafik Naccache, Derek H. Rosenzweig, Lisbet Haglund, Fiorenzo Vetrone, Marta Cerruti.Photocleavable Hydrogel-Coated Upconverting Nanoparticles: A Multifunctional Theranostic Platform for NIR Imaging and On-Demand Macromolecular Delivery. Journal of the American Chemical Society, 2016; DOI: 10.1021/jacs.5b12357

Purdue University: Nanowire Implants offer Remote-Controlled Drug Delivery: Applications: Spinal Cord Injuries; Chemotherapy

A team of researchers has created a new implantable drug-delivery system using nanowires that can be wirelessly controlled.

The nanowires respond to an electromagnetic field generated by a separate device, which can be used to control the release of a preloaded drug. The system eliminates tubes and wires required by other implantable devices that can lead to infection and other complications, said team leader Richard Borgens, Purdue University’s Mari Hulman George Professor of Applied Neuroscience and director of Purdue’s Center for Paralysis Research.

“This tool allows us to apply drugs as needed directly to the site of injury, which could have broad medical applications,” Borgens said. “The technology is in the early stages of testing, but it is our hope that this could one day be used to deliver drugs directly to spinal cord injuries, ulcerations, deep bone injuries or tumors, and avoid the terrible side effects of systemic treatment with steroids or chemotherapy.”

The team tested the drug-delivery system in mice with compression injuries to their spinal cords and administered the corticosteroid dexamethasone. The study measured a molecular marker of inflammation and scar formation in the central nervous system and found that it was reduced after one week of treatment. A paper detailing the results will be published in an upcoming issue of the Journal of Controlled Release and is currently available online.

IMAGE: An image of a field of polypyrrole nanowires captured by a scanning electron microscope is shown. A team of Purdue University researchers developed a new implantable drug-delivery system using the… view more

Credit: (Purdue University image/courtesy of Richard Borgens)

The nanowires are made of polypyrrole, a conductive polymer material that responds to electromagnetic fields. Wen Gao, a postdoctoral researcher in the Center for Paralysis Research who worked on the project with Borgens, grew the nanowires vertically over a thin gold base, like tiny fibers making up a piece of shag carpet hundreds of times smaller than a human cell. The nanowires can be loaded with a drug and, when the correct electromagnetic field is applied, the nanowires release small amounts of the payload. This process can be started and stopped at will, like flipping a switch, by using the corresponding electromagnetic field stimulating device, Borgens said.

The researchers captured and transported a patch of the nanowire carpet on water droplets that were used used to deliver it to the site of injury. The nanowire patches adhere to the site of injury through surface tension, Gao said.

The magnitude and wave form of the electromagnetic field must be tuned to obtain the optimum release of the drug, and the precise mechanisms that release the drug are not yet well understood, she said. The team is investigating the release process.

The electromagnetic field is likely affecting the interaction between the nanomaterial and the drug molecules, Borgens said.

“We think it is a combination of charge effects and the shape change of the polymer that allows it to store and release drugs,” he said. “It is a reversible process. Once the electromagnetic field is removed, the polymer snaps back to the initial architecture and retains the remaining drug molecules.”

For each different drug the team would need to find the corresponding optimal electromagnetic field for its release, Gao said.

This study builds on previous work by Borgens and Gao. Gao first had to figure out how to grow polypyrrole in a long vertical architecture, which allows it to hold larger amounts of a drug and extends the potential treatment period. The team then demonstrated it could be manipulated to release dexamethasone on demand. A paper detailing the work, titled “Action at a Distance: Functional Drug Delivery Using Electromagnetic-Field-Responsive Polypyrrole Nanowires,” was published in the journal Langmuir.

Other team members involved in the research include John Cirillo, who designed and constructed the electromagnetic field stimulating system; Youngnam Cho, a former faculty member at Purdue’s Center for Paralysis Research; and Jianming Li, a research assistant professor at the center.

For the most recent study the team used mice that had been genetically modified such that the protein Glial Fibrillary Acidic Protein, or GFAP, is luminescent. GFAP is expressed in cells called astrocytes that gather in high numbers at central nervous system injuries. Astrocytes are a part of the inflammatory process and form a scar tissue, Borgens said.

A 1-2 millimeter patch of the nanowires doped with dexamethasone was placed onto spinal cord lesions that had been surgically exposed, Borgens said. The lesions were then closed and an electromagnetic field was applied for two hours a day for one week. By the end of the week the treated mice had a weaker GFAP signal than the control groups, which included mice that were not treated and those that received a nanowire patch but were not exposed to the electromagnetic field. In some cases, treated mice had no detectable GFAP signal.

Whether the reduction in astrocytes had any significant impact on spinal cord healing or functional outcomes was not studied. In addition, the concentration of drug maintained during treatment is not known because it is below the limits of systemic detection, Borgens said.

“This method allows a very, very small dose of a drug to effectively serve as a big dose right where you need it,” Borgens said. “By the time the drug diffuses from the site out into the rest of the body it is in amounts that are undetectable in the usual tests to monitor the concentration of drugs in the bloodstream.”

Polypyrrole is an inert and biocompatable material, but the team is working to create a biodegradeable form that would dissolve after the treatment period ended, he said.

The team also is trying to increase the depth at which the drug delivery device will work. The current system appears to be limited to a depth in tissue of less than 3 centimeters, Gao said.

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The above post is reprinted from materials provided by Purdue University. The original item was written by Elizabeth K. Gardner. Note: Materials may be edited for content and length.

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Journal Reference:

1. Wen Gao, Richard Ben Borgens. Remote-controlled eradication of astrogliosis in spinal cord injury via electromagnetically-induced dexamethasone release from “smart” nanowires. Journal of Controlled Release, 2015; 211: 22 DOI: 10.1016/j.jconrel.2015.05.266

Nano-Sized Cancer Drug Delivery: One Step Closer

When you take a drug, it travels through your bloodstream, dissolving and dispersing, and eventually reaching its designated target area.

But because the blood containing the drug travels all round your body only a small percentage of the initial dose actually reaches the desired location.

For over-the-counter drugs like paracetamol or ibuprofen, with very few side-effects, this doesn’t matter too much.

But when it comes to cancer drugs, which can affect healthy cells just as much as cancer cells, this process can cause big problems.

Partly because drugs are diluted in their blood, cancer patients need to take these drugs in particularly high doses – and this can cause seriously unpleasant side effects.

But Professor Sonia Trigueros, co-director of the Oxford Martin Programme on Nanotechnology, is inching closer to developing a nano-scale drug delivery system with the aim of specifically targeting cancer cells.

Working with a team of chemists, engineers and physicists, Trigueros has embarked on an ambitious mission to tackle cancer at the ‘nano’ level – less than 100 nanometers wide. For context, this is super-tiny: a nanometre is a thousandth of a thousandth of a millimetre.

There’s still a long way to go, but Trigueros is making decent headway, and has recently tackled a major problem of working at a nano level. And at this year’s Wired Health conference – which looked at the future of health care, wellbeing and genomics – she told us about her recent progress, and her visions for the future.

At the nano level

Some of us will remember the periodic table displayed in our science classrooms which told us about the properties of each element. But working on a nano level everything changes, and elements behave completely differently.

Elements have different properties at the nano level than they do at the micro level, explained Prof Trigueros to the Wired Health 2015 audience.

This poses big problems for researchers trying to make nano-scale devices, which can be made out of a number of different materials, including gold, silver and carbon. All these materials are highly unstable at the nano level.

“After you make the nanostructures you only have minutes to a couple of days to work,” she said. They are really unstable, especially when you put them in water.”

This isn’t ideal, considering our bodies are made up mostly of water.

Credit: Professor Sonia Trigueros

Trigueros’ recent work has focused on trying to stabilise tiny tubes made of carbon, called carbon nanotubes, which hold drugs inside the tube so they can be delivered into cancer cells.

She has now found a way of keeping them stable for more than two years and in temperatures up to 42ºC.

To do this, she wraps DNA around the structures, like a tortilla wraps around the fillings of a burrito.

While this accomplishes the goal of keeping the nanostructures stable inside the body this doesn’t do much good if the DNA can’t unwrap to deliver the drugs. But, according to Trigueros, she has shown that, once inside a cell, the DNA easily unwinds and releases its payload.

Truly targeted drug delivery

So how does it all work? How do the drugs get into the cancer cells? Trigueros’s nanotubes exploit the differences between cancer cells and healthy cells – in this case, differences in the membranes that hold them together.

“Cancer cells are more permeable than normal cells so the nanotubes can get through the cell membrane. And once they are in, they unwrap and deliver drug,” explained Trigueros.

Exploiting differences in their permeability is one way to target the cancer cells, but Trigueros explains that there is more than one way to create a truly targeted drug delivery system.

“We can attach whatever we want on DNA,” she said. “So you can attach a protein that recognises cancer cells”.

From theory to reality

While this all sounds great in theory, will it actually work in reality?

Attaching proteins to DNA could create a truly targeted drug delivery system. Credit: Professor Sonia Trigueros

Trigueros has now started preliminary tests on laboratory grown lung cancer cells, she told us during an interview. And this has shown tentative promise, she says, citing unpublished data on their effectiveness at killing these cells in the lab.

Others are cautiously optimistic. “This is a really exciting prospect,” says Professor Duncan Graham, nanotechnology expert and advisor to Cancer Research UK.

“A common concern with carbon nanotubes is toxicity, but when coated with DNA this concern could be removed,” he explains, “and it also addresses a fundamental issue, which is that they collect into clusters that become a solid mass and so are unable to leave the body.”

In theory, once Trigueros’s nanotubes have finished their job they are tiny enough (50 nanometres) to be excreted through urine.

This isn’t the first time carbon nanotubes have been used in cancer research: a US research team has used them, for example, to target and collect images of tumours in mice. But the combination of drug delivery and cancer-specific targeting is what interests Professor Graham.

“Unlike previous work using carbon nanotubes, this approach is set to target the tumour specifically, potentially meaning fewer side effects and a lower dosage. I look forward to seeing this in animal models which is where the real proof of activity lies,” he said.

But he’s cautious, stressing that Trigueros’s work has not yet been peer-reviewed and published.

Next steps

Next Trigueros is aiming towards starting animal trials and, eventually, she wants to begin clinical trials in patients – that is if everything goes well.

She hopes to focus on how nanostructures could be used to cross the blood-brain barrier – the brain’s highly selective ‘bouncer’ that only lets certain molecules across. This has been notoriously difficult to get past, making targeting cancers in the brain more difficult.

But there is a still a long way to go and a lot of problems to tackle. In the shorter term, we’ll be keeping an eager eye on her drug delivery research, as her ideas continue to develop.

Explore further: Nano packages for anti-cancer drug delivery

Provided by Cancer Research UK

University of Waterloo: AmorChem Closes Nanotechnology-Drug Delivery Deal

Summary: University of Waterloo and AmorChem

AmorChem has closed its first transaction with the University of Waterloo. The project focuses on a mucoadhesive nanotechnology platform that supports the delivery of drugs, which is derived from the research work of Dr. Frank Gu. AmorChem said it will partner with Dr. Gu to pursue the preclinical development of a first product delivered using the technology. Based in Montréal, AmorChem is managed by Canadian venture capital firm GeneChem. The fund invests in R&D-stage initiatives to enable pre-clinical proof-of-concept in a semi-virtual mode.

AmorChem invests in a mucoadhesive nanoparticle drug delivery platform

Montreal, February 11, 2015 – AmorChem is pleased to announce the closing of a first transaction with the University of Waterloo. The project focuses on the use of a platform technology derived from the work of Dr. Frank Gu, Canada Research Chair in Nanotechnology Engineering, and Associate Professor in the Department of Chemical Engineering at the University of Waterloo. This mucoadhesive nanotechnology platform facilitates a directed and more efficacious delivery of drugs.

AmorChem will join forces with Dr. Gu in order to pursue the preclinical development of a first product delivered using this mucoadhesive nanoparticle technology. The choice of dry eye as an indication was driven by data which convinced us that delivering drug using these nanoparticles offers advantages which could improve the treatment of this disease,” explains Inès Holzbaur, general partner at AmorChem.

The nanoparticles bind to mucous membranes, allowing for targeted delivery of the treatment payload over a prolonged period of time. The size of the particles, combined with their mucoadhesive properties, make it possible to deliver large payloads that are released in a controlled manner while resisting the ocular clearance which typically occurs by drainage and tearing. It is expected that this will offer a treatment that is less toxic and allows for better compliance. Cyclosporin A, a drug known to be useful in the treatment of dry eye, will be the first molecule to be tested using this delivery system. Although this particular project is focused on an ophthalmic indication, the platform is also suited to nasal, pulmonary and gastro-intestinal delivery.

”Supported by commercialization leadership from the Waterloo Commercialisation Office, this is a strong validation of Dr. Gu’s translational research impact and the strength of nanotechnology engineering in general at the University of Waterloo. We believe AmorChem’s investment, under its flexible and supportive business model, will pave the way to successful commercialization of this transformative technology,” says D. Georges Dixon, vicepresident, research, University of Waterloo.

“Although AmorChem focuses on investments in the province of Quebec, this collaboration with an Ontarian institution shows that the AmorChem model is adaptable to other regions, and that there is demand for our kind of translational investing outside Quebec. We believe that out-of-province opportunities could play an interesting role in the future activities of AmorChem. For example, investments in platforms such as Dr. Gu’s may allow us to start-up companies in collaboration with Quebec-based venture capital funds,” concludes Elizabeth Douville, general partner at AmorChem.

ABOUT AMORCHEM L.P. AmorChem L.P. (www.amorchem.com) is a venture capital fund located in Montreal focused on primarily investing in promising life science projects originating from Quebec-based universities and research centres. The principal limited partners of this fund are Investissement-Québec, FIER Partenaires, Fonds de solidarité FTQ and Merck & Co. This fund is the latest addition to the GeneChem portfolio of funds, a fund manager in existence since 1997. AmorChem’s innovative business model involves financing research-stage projects to enable them to reach pre-clinical proof-of-concept (“POC”) in a semi-virtual mode within 18-24 months. The fund seeks to generate returns through a two-pronged exit strategy: sell projects having reached POC to large biotechnology or pharmaceutical companies; or bundle them into new spin-out companies. AmorChem using external resources will manage the projects. To that effect, AmorChem has established a strategic partnership with the Biotechnology Research Institute in order to access its R&D platforms. In addition, to enabling projects requiring small molecules as tools or drug leads, AmorChem has founded NuChem Therapeutics Inc., a medicinal chemistry contract-research company.

Nano packages for anti-cancer drug delivery

Cancer stem cells are resistant to chemotherapy and consequently tend to remain in the body even after a course of treatment has finished, where they can often trigger cancer recurrence or metastasis. A new study by researchers from the A*STAR Institute of Bioengineering and Nanotechnology has found that using nanoparticles to deliver an anti-cancer drug that simultaneously kills cancer cells and cancer stem cells significantly reduces the recurrence and metastasis of lung cancer.

The drug phenformin is very effective against cancer stem cells. It is related to the popular anti-diabetic drug metformin but is 50 times more potent against cancer cell lines. However, phenformin is too toxic in its free form to be administered to patients at the doses required to kill both normal cancer cells and cancer stem cells. Now, Yi Yan Yang and her colleagues at the Institute of Bioengineering and Nanotechnology in Singapore have found a way to overcome this problem — using self-assembling polymer nanoparticles to deliver the drug (“Phenformin-loaded polymeric micelles for targeting both cancer cells and cancer stem cells in vitro and in vivo”).

Phenformin-loaded nanoparticles kill both cancer cells and cancer stem cells, leading to tumor regression. (Image: A*STAR Institute of Bioengineering and Nanotechnology)

In the first study to use polymer nanoparticles to deliver phenformin to target both cancer cells and cancer stem cells, Yang and co-workers found that phenformin-loaded nanoparticles targeted both kinds of cancer cells in a mouse model of human lung cancer.

The nanoparticles released the drug in a sustained manner due to their hydrophilic shells, which “prevent enzymatic degradation of the cargo and protein adsorption onto the nanoparticles,” explains Yang. “This also prolongs blood circulation so that the cargo-loaded nanoparticles have enough time to accumulate in tumor tissues.”

This delivery method enabled Yang and her team to arrest the growth of cancer and cancer stem cells when the nanoparticles were delivered to implanted human lung cancer in mice.

“The results showed that the phenformin-loaded nanoparticles were more effective than free phenformin in inhibiting the growth of both cancer stem cells and normal cancer cells,” Yang says. Moreover, the nanoparticles did not induce the liver toxicity observed in systemically administered phenformin.

The method can also be extended to other drugs. The team has used the nanoparticle-based delivery system in a mouse model of human breast cancer to deliver the anti-cancer drug, doxorubicin — another drug that is toxic at certain doses but is capable of killing cancer stem cells. “The combination shrank tumors by more than 40 per cent and was more effective than treatment with either drug alone,” says Yang.

The team is now seeking to collaborate with pharmaceutical companies to bring this technology to human clinical trials.

Source: A*STAR

Read more: Nano packages for anti-cancer drug delivery

Smart Cancer Nanotheranostics

(Nanowerk Spotlight) Cancer is one of the leading  causes of death in the world and remains a difficult disease to treat. Current  problems associated with conventional cancer chemotherapies include insolubility  of drugs in aqueous medium; delivery of sub-therapeutic doses to target cells;  lack of bioavailability; and most importantly, non-specific toxicity to normal  tissues. Recent contributions of nanotechnology research address possible  solutions to these conundrums. Nevertheless, challenges remain with respect to  delivery to specific sites, real time tracking of the delivery system, and  control over the release system after the drug has been transported to the  target site.

Nanomedical research on nanoparticles is exploring these issues  and has already been showing potential solutions for cancer diagnosis and  treatment. But a heterogeneous disease like cancer requires smart approaches  where therapeutic and diagnostic platforms are integrated into a theranostic  approach.

Theranostics – a combination of the words therapeutics and diagnostics – describes a treatment platform that combines a  diagnostic test with targeted therapy based on the test results, i.e. a step  towards personalized medicine. Making use of nanotechnology materials and  applications, theranostic nanomedicine can be understood as an integrated  nanotherapeutic system, which can diagnose, deliver targeted therapy and monitor  the response to therapy.

Theranostic nanomedicine has the potential for simultaneous and  real time monitoring of drug delivery, trafficking of drug and therapeutic  responses.

Our Smart Materials and Biodevice group at the Biosensors and Bioelectronics Centre, Linkoping University,  Sweden, has demonstrated for the first time a MRI-visual order-disorder micellar nanostructures for smart  cancer theranostics.

        The  drug release mechanism via functional outcome of the pH response illustrated in  the schematic diagram. (Image: Smart Materials and Biodevice group, Linköping  University)   In the report, we fabricated a novel pH-triggered tumour  microenvironment sensitive order-disorder nanomicelle platform for smart  theranostic nanomedicine.             

The real-time monitoring of drug distribution will help  physicians to assess the type and dosage of drug for each patient and thus will  prevent overdose that could result in detrimental side-effects, or suboptimal  dose that could lead to tumour progression.

Additionally, the monitoring of normal healthy tissues by  differentiating with the MRI contrast will help balance the estimation of lethal  dose (for normal tissue) and pharmacologically active doses (for tumour). As a  result, this will help to minimize off-target effects and enhance effective  treatment.

In the present report, the concurrent therapy by doxorubicin and  imaging strategies by superparamagnetic iron oxide nanoparticles with our smart  architecture will provide every detail and thus can enable stratification of  patients into categorized responder (high/medium/low), and has the potential to  enhance the clinical outcome of therapy.

It shows, for the first time, concentration dependent  T2-weighted MRI contrast for a monolayer of clustered cancer cells. The pH  tunable order-disorder transition of the core-shell structure induces the  relative changes in MRI that will be sensitive to tumour microenvironment and  stages.

     A  novel MRI visual order-disorder nanostructure for cancer nanomedicine explores  pH-trigger mechanism for theranostics of tumour hallmark functions. The pH  tunable order-disorder transition induces the relative changes in MRI contrast.  The outcome elucidates the potential of this material for smart cancer  theranostics by delivering non-invasive real-time diagnosis, targeted therapy  and monitoring the course and response of the action. (Image: Smart Materials  and Biodevice group, Linköping University)

Our findings illustrate the potential of these biocompatible  smart theranostic micellar nanostructures as a nontoxic, tumour-target specific,  tumour-microenvironment sensitive, pH-responsive drug delivery system with  provision for early stage tumour sensing, tracking and therapy for cells  over-expressed with folate receptors. The outcomes elucidate the potential of  smart cancer theranostic nanomedicine in non-invasive real-time diagnosis,  targeted therapy and monitoring of the course and response of the action before,  during and after treatment regimen.

By Hirak K Patra, Nisar Ul Khali, Thobias Romu, Emilia  Wiechec, Magnus Borga, Anthony PF Turner and Ashutosh Tiwari, Biosensors and Bioelectronics Centre,  Linköping University, Sweden

Read more: http://www.nanowerk.com/spotlight/spotid=33186.php#ixzz2kTi8huZB

New theranostic nanoparticle delivers, tracks cancer drugs

(Nanowerk News) University of New South Wales (UNSW)  chemical engineers have synthesised a new iron oxide nanoparticle that delivers  cancer drugs to cells while simultaneously monitoring the drug release in real  time.

The result, published online in the journal ACS Nano (“Using Fluorescence Lifetime Imaging Microscopy to  Monitor Theranostic Nanoparticle Uptake and Intracellular Doxorubicin  Release”), represents an important development for the emerging field of  theranostics – a term that refers to nanoparticles that can treat and diagnose  disease.

“Iron oxide nanoparticles that can track drug delivery will  provide the possibility to adapt treatments for individual patients,” says  Associate Professor Cyrille Boyer from the UNSW School of Chemical Engineering.

By understanding how the cancer drug is released and its effect  on the cells and surrounding tissue, doctors can adjust doses to achieve the  best result.

Importantly, Boyer and his team demonstrated for the first time  the use of a technique called fluorescence lifetime imaging to monitor the drug  release inside a line of lung cancer cells.

“Usually, the drug release is determined using model experiments  on the lab bench, but not in the cells,” says Boyer. “This is significant as it  allows us to determine the kinetic movement of drug release in a true biological  environment.”

Magnetic iron oxide nanoparticles have been studied widely  because of their applications as contrast agents in magnetic resonance imaging,  or MRI. Several recent studies have explored the possibility of equipping these  contrast agents with drugs.

However, there are limited studies describing how to load  chemotherapy drugs onto the surface of magnetic iron oxide nanoparticles, and no  studies that have effectively proven that these drugs can be delivered inside  the cell. This has only been inferred.

With this latest study, the UNSW researchers engineered a new  way of loading the drugs onto the nanoparticle’s polymer surface, and  demonstrated for the first time that the particles are delivering their drug  inside the cells.

“This is very important because it shows that bench chemistry is  working inside the cells,” says Boyer. “The next step in the research is to move  to in-vivo applications.”

Source: University of New South Wales

Read more: http://www.nanowerk.com/news2/newsid=32972.php#ixzz2j9WI0HAR

Nanodiamonds: a cancer patient’s best friend?

(Nanowerk News) Diamonds are sometimes considered as a  girl’s best friend. Now, this expression is about to have a new meaning. Indeed,  nanometric scale diamond particles could offer a new way to detect cancer far  earlier than previously thought. This is precisely the objective of a research project  called Dinamo, funded by the EU. Specifically, it aims to develop a  non-invasive nanotechnology sensing platform for real-time monitoring of  biomolecular processes in living cancer cells.

To do so, they developed a new technique, based on the use of  fluorescent nanodiamond particles (NDPs). “We demonstrated that the specific  combination of NDP-properties make them a highly suitable material for the  construction of probes capable of sensing biomolecules ranging from proteins to  DNA,” says team coordinator Milos Nesladek, who is also principle scientist at  the Institute for Material Research, Imec, based in Leuven, Belgium, “such  probes could be used to study molecular processes in cells at nanoscale.”

The trouble is that previous solutions did not allow monitoring  processes within living cells for any extended period of time. “Our key  challenge was to replace fluorescent bimolecular dyes that are currently used as  luminescence markers in cancer cell research,” explains Nesladek.

NDPs present several advantages. They are highly biocompatible.  They can remain for prolonged periods inside cells without influencing any  cellular mechanisms. Furthermore, they can be engineered to obtain a range of  optic, magnetic and surface properties. “The small size of NDPs enables them to  penetrate individual cell membranes in a non-invasive way, which causes no  damage to the cell and without any disruption of normal cellular functions,”  Nesladek tells CommNet. “The luminescence and the magnetic properties change  depending on the NDP’s interaction with the cellular environment,” he adds.

The surface properties of NDPs are such that it is possible to  attach specific biomolecules to them, such as primary DNA molecules. Delivered  precisely to the target cell, these biomolecules can measure, monitor or alter  biological components within the cell. The NDPs can thus become not only a tool  to monitor and detect pre-cancerous changes, but also to rectify them. Further  developments are going on in subsequent EU-projects such as DIAMANT.

Some experts welcome this approach. “Development of new drug  delivery carriers is crucial for treatment of numerous deceases, including  cancer,” comments Fedor Jelezko, director of the Institute of Quantum Optics at  Ulm University in Germany. “The novelty of approach in [the project] is the use  of innovative material to transport drugs,” he tells CommNet. Nanodiamond  provides unique opportunities for drug carrier design since they can be imaged  optically using fluorescence microscopy technique. “This allows monitoring of  drug delivery and release of drugs in the cells with unprecedented details,” he  adds. This monitoring has already been demonstrated (“Nanodiamond as a Vector for siRNA Delivery to Ewing Sarcoma  Cells”) by teams of the Ecole Normale Supérieure (ENS) in Cachan and Gustave  Roussy Cancer Institute in Paris, France.

Other experts are more cautious. “Although there have been  numerous convincing experiments showing that nanodiamonds can carry active  anti-cancer drugs in culture cells and even in mice, it is very unlikely that it  will be ever used in humans, mostly because diamond is so inert that it cannot  be degraded and therefore cannot be easily eliminated by the body”, comments  François Treussart, physics professor at the ENS.

However, he seems a bright future for the technology. “Far  beyond the [project] goals, nanodiamond future in medical applications is more  as a diagnostic device in personal medicine or as a monitoring tool for example  to track stem cell engraftment in regenerative medicine, as recently  demonstrated (“Tracking the engraftment and regenerative  capabilities of transplanted lung stem cells using fluorescent  nanodiamonds”) by the biomedical applications of fluorescent ND-team at the  Institute of Atomic and Molecular Science, at the Academia Sinica inTaiwan,” he  concludes.

A NDP-probe, placed in a target cell, should be able to detect  and relay information about the processes taking place in this cell. “The Dinamo  project has been finished, but the partners still are collaborating,” Nesladek  tells. “The University of Stuttgart in Germany is developing a NDP-probe.  “Dinamo has focused on the context of breast cancer and colorectal cancer, but  there is no reason why the technique could not be applied to a wide range of  other cancers,” he tells CommNet. He concludes that another future aim is to  explore the possibility of using NDP probes to detect cancer stem cells.

Source: By Koen Mortelmans, Youris

Read more: http://www.nanowerk.com/news2/newsid=32873.php#ixzz2iZP7drvc

Nanotech system, cellular heating may improve treatment of ovarian cancer

Oct 17, 2013 

    

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 A new drug delivery system that incorporates heat, nanotechnology and chemotherapy shows promise in improving the treatment of ovarian cancer. Credit: Oregon State University

The combination of heat, chemotherapeutic drugs and an innovative delivery system based on nanotechnology may significantly improve the treatment of ovarian cancer while reducing side effects from toxic drugs, researchers at Oregon State University report in a n

The findings, so far done only in a laboratory setting, show that this one-two punch of mild hyperthermia and chemotherapy can kill 95 percent of ovarian cancer cells, and scientists say they expect to improve on those results in continued research.

The work is important, they say, because ovarian cancer – one of the leading causes of cancer-related deaths in women – often develops resistance to chemotherapeutic drugs if it returns after an initial remission. It kills more than 150,000 women around the world every year.

“Ovarian cancer is rarely detected early, and because of that chemotherapy is often needed in addition to surgery,” said Oleh Taratula, an assistant professor in the OSU College of Pharmacy. “It’s essential for the chemotherapy to be as effective as possible the first time it’s used, and we believe this new approach should help with that.”

It’s known that elevated temperatures can help kill cancer cells, but heating just the cancer cells is problematic. The new system incorporates the use of iron oxide nanoparticles that can be coated with a cancer-killing drug and then heated once they are imbedded in the cancer cell.

Other features have also been developed to optimize the new system, in an unusual collaboration between engineers, material science experts and pharmaceutical researchers.

A peptide is used that helps guide the nanoparticle specifically to cancer cells, and the nanoparticle is just the right size – neither too big nor too small – so the immune system will not reject it. A special polyethylene glycol coating further adds to the “stealth” effect of the nanoparticles and keeps them from clumping up. And the interaction between the cancer drug and a polymer on the nanoparticles gets weaker in the acidic environment of cancer cells, aiding release of the drug at the right place.

“The hyperthermia, or heating of cells, is done by subjecting the magnetic nanoparticles to an oscillating, or alternating magnetic field,” said Pallavi Dhagat, an associate professor in the OSU School of Electrical Engineering and Computer Science, and co-author on the study. “The nanoparticles absorb energy from the oscillating field and heat up.”

The result, in laboratory tests with ovarian cancer cells, was that a modest dose of the chemotherapeutic drug, combined with heating the cells to about 104 degrees, killed almost all the cells and was far more effective than either the drug or heat treatment would have been by itself.

Doxorubicin, the cancer drug, by itself at the level used in these experiments would leave about 70 percent of the cancer cells alive. With the new approach, only 5 percent were still viable.

The work was published in the International Journal of Pharmaceutics, as a collaboration of researchers in the OSU College of Pharmacy, College of Engineering, and Ocean NanoTech of Springdale, Ark. It was supported by the Medical Research Foundation of Oregon, the PhRMA Foundation and the OSU College of Pharmacy.

“I’m very excited about this delivery system,” Taratula said. “Cancer is always difficult to treat, and this should allow us to use lower levels of the toxic chemotherapeutic drugs, minimize side effects and the development of drug resistance, and still improve the efficacy of the treatment. We’re not trying to kill the cell with heat, but using it to improve the function of the drug.”

Iron oxide particles had been used before in some medical treatments, researchers said, but not with the complete system developed at OSU. Animal tests, and ultimately human trials, will be necessary before the new system is available for use.

Drug delivery systems such as this may later be applied to other forms of cancer, such as prostate or pancreatic cancer, to help improve the efficacy of chemotherapy in those conditions, Taratula said.

Explore further:     New ovarian cancer treatment succeeds in the lab

Read more at: http://phys.org/news/2013-10-nanotech-cellular-treatment-ovarian-cancer.html#jCp

Read more at: http://phys.org/news/2013-10-nanotech-cellular-treatment-ovarian-cancer.html#jCp