Tag Archives: #microbubbles

Scientists Use Tiny Bubbles To Help Treat Common Childhood Cancer (Medicine)

Researchers at UCL have developed a new way to deliver drugs that can shut down cancer-promoting mutations in neuroblastoma. The findings in mice, show the method, which uses tiny bubbles to deliver therapies directly to tumour cells, reduced tumour growth and improved survival.

Neuroblastoma is the most common solid tumour found in children and accounts for about 15% of all cancer-related deaths in children. Tumours develop from certain types of nerve cells and are most commonly found in the abdomen. Children who are diagnosed above the age of one often fail to respond to treatment or relapse at a later time, meaning that there is an urgent need for new treatment options. 

The research, published in Advanced Functional Materials and funded by Worldwide Cancer Research, now offers a new potential treatment approach. MYCN is a gene that is associated with poor prognosis and is found to be mutated or overactive in about 20% of neuroblastoma cases. The gene is usually expressed during foetal development and is involved in cell growth and development. Neuroblastoma cells continue to express too much MYCN, leading to uncontrolled cell growth and division and preventing cancer cells from dying.

Researchers at UCL Great Ormond Street Institute of Child Health have now found a way to silence MYCN by delivering a certain type of genetic material called siRNA, directly to the tumour cells. They developed nanoparticles – or tiny bubbles – that use the leaky blood vessels around the tumour and certain features that are only present on tumour cells to home in on the tumours.

The vast majority of nanoparticles, which were delivered via injection, located to the tumour and successfully shut down the MYCN gene causing the cancer. The treatment caused the tumours to grow at a slower pace and prolonged the time that the mice survived the cancer.

Senior author, Professor Stephen Hart, UCL GOS ICH, said: “These findings show that this approach with MYCN siRNA delivered by a nanoparticle is a new potential therapy for neuroblastoma. The next steps would be to develop methods of scaling up production to clinical grade, and to show that the treatment is safe. Current therapies such as surgery, radio and chemotherapy are effective at removing the primary tumour but, unfortunately, in many cases the tumour will return at other sites in the body, which is much harder to treat. We hope that this therapy might augment conventional therapies and provide a way of targeting the therapy to these new tumour sites.”

Dr Helen Rippon, Chief Executive at Worldwide Cancer Research said: “Each year about 100 families in the UK receive the devastating news that their child has developed neuroblastoma. Unfortunately, the cancer is often detected at a relatively late stage and intense treatment is needed.

“We are funding researchers, like Professor Hart, to start new cancer cures and this innovative research shows just how important investment in early-stage discovery research is. Using new methods, such as nanoparticles, to deliver treatment straight to the heart of cancer is an incredibly exciting area of research. These new results now offer hope to patients and their families by paving the way for effective new treatment options.”

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  • UCL Great Ormond Street Institute of Child Health

Provided by UCL

Using Targeted Microbubbles to Administer Toxic Cancer Drugs (Medicine)

University of Leeds research has shown how microbubbles carrying powerful cancer drugs can be guided to the site of a tumour using antibodies.

Microbubbles carry the anticancer drug to the site of the tumour. Antibodies attached to the microbubbles are attracted to the growth hormone found around cancer cells. Once in situ, an unltrasound device is used to burst the bubbles, releasing the drug. Image credit: Dr Sunjie Ye, University of Leeds

Microbubbles are small manufactured spheres half the size of a red blood cell – and scientists believe they can be used to transport drugs to highly specific locations within the body.  

The findings are published in the journal Theranostics. 

Microbubbles could allow us to use powerful drugs with precision – that reduces the risk of damaging healthy cells.” said Dr. Nicola Ingram, University of Leeds.

The lead authors, Drs Nicola Ingram and Laura McVeigh from the School of Medicine, describe how they targeted microbubbles through the use of a ‘navigational aid’ – antibodies attracted to the growth hormone found in high levels in the blood vessels supplying a tumour. 

The antibodies were attached to the microbubbles. As a result of being attracted to the growth hormone, the microbubbles became concentrated at the site of the tumour. A pulse from an ultrasound device was used to burst open the microbubbles, and that released the anti-cancer agent. 

The study was conducted on animals, which were used as a model to try and develop this technique for use in humans.

Dr Ingram said being able to deliver anticancer drugs in a very targeted fashion would be a major advance in cancer therapy.  

She added: “One of the big problems with cancer drugs is that they are highly toxic to the rest of the body too. Microbubble technology could allow us to use these very powerful drugs with precision and that reduces the risk of the drug damaging healthy cells nearby. 

“It is about finely focused drug delivery.” 

The study also revealed that by attaching the drug directly to the microbubbles allowed it to circulate in the body for longer, increasing delivery into the tumour – in effect making the drug more potent.   

As a result, the scientists were able to slow cancer growth with a much smaller drug dose.  

Professor Stephen Evans, head of the Molecular and Nanoscale Physics Group at Leeds and one of the paper’s authors, said: “The results of this study are exciting because we not only show the very precise and targeted way microbubbles can be guided to cancer sites but that the efficacy of drug delivery is substantially improved, opening the way to use highly toxic drugs to fight cancer, without the harmful side effects. 

“Put simply: you get more bang for your buck.” 

Watch the video where Professor Evans describes the potential benefit of microbubble technology

The next stage of the research is to look at using microbubbles to develop targeted, triggered, delivery systems in patients for the diagnosis and treatment of advanced colorectal cancer, the third most common cancer in the UK.  

Co-author Professor Peter Simpson, Chief Scientific Officer at Medicines Discovery Catapult said: “Complex medicines have the potential to be the third wave of medicines, addressing patients’ problems which conventionally administered small molecules and monoclonal antibodies cannot.  

“This project is a very encouraging example of exploring how using an advanced drug delivery technology could improve biodistribution, targeting and efficacy of a potentially toxic therapeutic.” 

This study involved a research team from the universities of Leeds, Bradford, Manchester, and the Medicines Discovery Catapult in Cheshire. The study and a follow-on study were funded by the Engineering and Physical Sciences Research Council. In addition, several PhD students are also developing microbubbles for treatment of other diseases and have been funded by University of Leeds alumni.

The paper is titled: ‘Ultrasound-triggered therapeutic microbubbles enhance the efficacy of cytotoxic drugs by increasing circulation and tumor drug accumulation and limiting bioavailability and toxicity in normal tissues’ and published in the journal Theranostics.

The University of Leeds has established the Leeds Microbubble Consortium, a group of cancer scientists, engineers, physicists and chemists to develop ways microbubble technology could enhance cancer treatment.

Provided by University of Leeds

Graphene Microbubbles Make Perfect Lenses (Material Science)

New method generates precisely controlled graphene microbubbles with perfectly spherical curvature for lenses.

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.

Photonic jet focused by a graphene oxide microbubble lens. ©H. Lin et al.

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.

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

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.”

References: Han Lin et al., “Near perfect microlenses based on graphene microbubbles,” Adv. Photon. 2(5), 055001, doi 10.1117/1.AP.2.5.055001. Link: https://www.spiedigitallibrary.org/journals/advanced-photonics/volume-2/issue-05/055001/Near-perfect-microlenses-based-on-graphene-microbubbles/10.1117/1.AP.2.5.055001.full?SSO=1

Provided by SPIE