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Home > Press > NTU scientists invent bubble technology which can shoot drugs deep into tumors: Using ultrasound, drug particles can be directed to a specific area Abstract: Scientists at Nanyang Technological University (NTU Singapore) have invented a new way to deliver cancer drugs deep into tumour cells. The NTU scientists create micro-sized gas bubbles coated with cancer drug particles and iron oxide nanoparticles, and then use magnets to direct these bubbles to gather around a specific tumour. Ultrasound is then used to vibrate the microbubbles, providing the energy to direct the drug particles into a targeted area. This innovative technique was developed by a multidisciplinary team of scientists, led by Asst Prof Xu Chenjie from the School of Chemical and Biomedical Engineering and Assoc Prof Claus-Dieter Ohl from the School of Physical and Mathematical Sciences. NTU's microbubbles were successfully tested in mice and the study has been published by the Nature Publishing Group in Asia Materials, the top journal for materials sciences in the Asia-Pacific region. Overcoming limitations of chemotherapy Asst Prof Xu, who is also a researcher at the NTU-Northwestern Institute for Nanomedicine, said their new method may solve some of the most pressing problems faced in chemotherapy used to treat cancer. The main issue is that current chemotherapy drugs are largely non-targeted. The drug particles flow in the bloodstream, damaging both healthy and cancerous cells. Typically, these drugs are flushed away quickly in organs such as the lungs and liver, limiting their effectiveness. The remaining drugs are also unable to penetrate deep into the core of the tumour, leaving some cancer cells alive, which could lead to a resurgence in tumour growth. "The first unique characteristic of our microbubbles is that they are magnetic. After injecting them into the bloodstream, we are able to gather them around the tumour using magnets and ensure that they don't kill the healthy cells," explains Asst Prof Xu, who has been working on cancer diagnosis and drug delivery systems since 2004. "More importantly, our invention is the first of its kind that allows drug particles to be directed deep into a tumour in a few milliseconds. They can penetrate a depth of 50 cell layers or more - which is about 200 micrometres, twice the width of a human hair. This helps to ensure that the drugs can reach the cancer cells on the surface and also inside the core of the tumour." Clinical Associate Professor Chia Sing Joo, a Senior Consultant at the Tan Tock Seng Hospital's Endoscopy Centre and the Urology & Continence Clinic, was one of the consultants for this study. A trained robotic surgeon experienced in the treatment of prostate, bladder and kidney cancer, Assoc Prof Chia said, "For anticancer drugs to achieve their best effectiveness, they need to penetrate into the tumour efficiently in order to reach the cystoplasm of all the cancer cells that are being targeted without affecting the normal cells. "Currently, these can be achieved by means of a direct injection into the tumour or by administering a large dosage of anticancer drugs, which can be painful, expensive, impractical and might have various side effects." The specialist in Uro-oncology added that if NTU's technology proves to be viable, clinicians might be able to localise and concentrate the anticancer drugs around a tumour, and introduce the drugs deep into tumour tissues in just a few seconds using a clinical ultrasound system. "If successful, I envisage it can be a good alternative treatment in the future, one which is low cost and yet effective for the treatment of cancers involving solid tumours, as it might minimise the side effects of drugs." New drug delivery system The motivation for this research project is to find alternative solutions for drug delivery systems that are non-invasive and safe. Ultrasound uses soundwaves with frequencies higher than those heard by the human ear. It is commonly used for medical imaging such as to get diagnostic images. Magnets, which can draw and attract the microbubbles, are already in use in diagnostic machines such the Magnetic Resonance Imaging (MRI). "We are looking at developing novel drug carriers - essentially better ways of delivering drugs with minimum side effects," explained Prof Ohl, an expert in biophysics who had published previous studies involving drug delivery systems and bubble dynamics. "Most prototype drug delivery systems on the market face three main challenges before they can be commercially successful: they have to be non-invasive, patient-friendly and yet cost-effective. "Using the theory of microbubbles and how their surface vibrates under ultrasound, we were able to come up with our solution that addresses these three challenges." Interdisciplinary team This study, which took two and a half years, involved a 12-man international interdisciplinary team consisting of NTU scientists as well as scientists from City University of Hong Kong and Tel Aviv University in Israel. Two NTU undergraduates doing their Final Year Project and one student in Summer Research Internship Programme (NTU) were also part of the team. Moving forward, the team will be adopting this new drug delivery system in studies on lung and liver cancer using animal models, and eventually clinical studies. They estimate that it will take another eight to ten years before it reaches human clinical trials. About Nanyang Technological University A research-intensive public university, Nanyang Technological University, Singapore (NTU Singapore) has 33,500 undergraduate and postgraduate students in the colleges of Engineering, Business, Science, Humanities, Arts, & Social Sciences, and its Interdisciplinary Graduate School. It has a new medical school, the Lee Kong Chian School of Medicine, set up jointly with Imperial College London. NTU is also home to world-class autonomous institutes - the National Institute of Education, S Rajaratnam School of International Studies, Earth Observatory of Singapore, and Singapore Centre for Environmental Life Sciences Engineering - and various leading research centres such as the Nanyang Environment & Water Research Institute (NEWRI), Energy Research Institute @ NTU and the Institute on Asian Consumer Insight (ACI). Ranked 13th in the world, NTU has also been ranked the world's top young university for the last two years running. The University's main campus has been named one of the Top 15 Most Beautiful in the World. NTU also has a campus in Novena, Singapore's medical district. For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.


News Article | April 19, 2016
Site: www.biosciencetechnology.com

Scientists at Nanyang Technological University (NTU Singapore) have invented a new way to deliver cancer drugs deep into tumor cells. The NTU scientists create micro-sized gas bubbles coated with cancer drug particles and iron oxide nanoparticles, and then use magnets to direct these bubbles to gather around a specific tumor. Ultrasound is then used to vibrate the microbubbles, providing the energy to direct the drug particles into a targeted area. This innovative technique was developed by a multidisciplinary team of scientists, led by Asst Prof Xu Chenjie from the School of Chemical and Biomedical Engineering and Assoc Prof Claus-Dieter Ohl from the School of Physical and Mathematical Sciences. NTU's microbubbles were successfully tested in mice and the study has been published by the Nature Publishing Group in Asia Materials, the top journal for materials sciences in the Asia-Pacific region. Asst Prof Xu, who is also a researcher at the NTU-Northwestern Institute for Nanomedicine, said their new method may solve some of the most pressing problems faced in chemotherapy used to treat cancer. The main issue is that current chemotherapy drugs are largely non-targeted. The drug particles flow in the bloodstream, damaging both healthy and cancerous cells. Typically, these drugs are flushed away quickly in organs such as the lungs and liver, limiting their effectiveness. The remaining drugs are also unable to penetrate deep into the core of the tumor, leaving some cancer cells alive, which could lead to a resurgence in tumor growth. "The first unique characteristic of our microbubbles is that they are magnetic. After injecting them into the bloodstream, we are able to gather them around the tumour using magnets and ensure that they don't kill the healthy cells," explains Asst Prof Xu, who has been working on cancer diagnosis and drug delivery systems since 2004. "More importantly, our invention is the first of its kind that allows drug particles to be directed deep into a tumor in a few milliseconds. They can penetrate a depth of 50 cell layers or more - which is about 200 micrometres, twice the width of a human hair. This helps to ensure that the drugs can reach the cancer cells on the surface and also inside the core of the tumour." Clinical Associate Professor Chia Sing Joo, a Senior Consultant at the Tan Tock Seng Hospital's Endoscopy Centre and the Urology & Continence Clinic, was one of the consultants for this study. A trained robotic surgeon experienced in the treatment of prostate, bladder and kidney cancer, Assoc Prof Chia said, "For anticancer drugs to achieve their best effectiveness, they need to penetrate into the tumor efficiently in order to reach the cystoplasm of all the cancer cells that are being targeted without affecting the normal cells. "Currently, these can be achieved by means of a direct injection into the tumor or by administering a large dosage of anticancer drugs, which can be painful, expensive, impractical and might have various side effects." The specialist in Uro-oncology added that if NTU's technology proves to be viable, clinicians might be able to localize and concentrate the anticancer drugs around a tumor, and introduce the drugs deep into tumor tissues in just a few seconds using a clinical ultrasound system. "If successful, I envisage it can be a good alternative treatment in the future, one which is low cost and yet effective for the treatment of cancers involving solid tumors, as it might minimize the side effects of drugs." The motivation for this research project is to find alternative solutions for drug delivery systems that are non-invasive and safe. Ultrasound uses soundwaves with frequencies higher than those heard by the human ear. It is commonly used for medical imaging such as to get diagnostic images. Magnets, which can draw and attract the microbubbles, are already in use in diagnostic machines such the Magnetic Resonance Imaging (MRI). "We are looking at developing novel drug carriers - essentially better ways of delivering drugs with minimum side effects," explained Prof Ohl, an expert in biophysics who had published previous studies involving drug delivery systems and bubble dynamics. "Most prototype drug delivery systems on the market face three main challenges before they can be commercially successful: they have to be non-invasive, patient-friendly and yet cost-effective. "Using the theory of microbubbles and how their surface vibrates under ultrasound, we were able to come up with our solution that addresses these three challenges." This study, which took two and a half years, involved a 12-man international interdisciplinary team consisting of NTU scientists as well as scientists from City University of Hong Kong and Tel Aviv University in Israel. Two NTU undergraduates doing their Final Year Project and one student in Summer Research Internship Programme (NTU) were also part of the team. Moving forward, the team will be adopting this new drug delivery system in studies on lung and liver cancer using animal models, and eventually clinical studies. They estimate that it will take another eight to ten years before it reaches human clinical trials.


News Article | February 4, 2016
Site: phys.org

The two new satellites launched by Nanyang Technological University, Singapore (NTU Singapore) two months ago have successfully completed their first space missions.


News Article | April 18, 2016
Site: www.cemag.us

Scientists at Nanyang Technological University (NTU) have invented a new way to deliver cancer drugs deep into tumor cells. The NTU scientists create micro-sized gas bubbles coated with cancer drug particles and iron oxide nanoparticles, and then use magnets to direct these bubbles to gather around a specific tumor. Ultrasound is then used to vibrate the microbubbles, providing the energy to direct the drug particles into a targeted area. This innovative technique was developed by a multidisciplinary team of scientists, led by Assistant Professor Xu Chenjie from the School of Chemical and Biomedical Engineering and Associate Professor Claus-Dieter Ohl from the School of Physical and Mathematical Sciences. NTU’s microbubbles were successfully tested in mice and the study has been published by the Nature Publishing Group in Asia Materials, the top journal for materials sciences in the Asia-Pacific region. Xu, who is also a researcher at the NTU-Northwestern Institute for Nanomedicine, says their new method may solve some of the most pressing problems faced in chemotherapy used to treat cancer. The main issue is that current chemotherapy drugs are largely non-targeted. The drug particles flow in the bloodstream, damaging both healthy and cancerous cells. Typically, these drugs are flushed away quickly in organs such as the lungs and liver, limiting their effectiveness. The remaining drugs are also unable to penetrate deep into the core of the tumor, leaving some cancer cells alive, which could lead to a resurgence in tumor growth. “The first unique characteristic of our microbubbles is that they are magnetic. After injecting them into the bloodstream, we are able to gather them around the tumor using magnets and ensure that they don’t kill the healthy cells,” explains Xu, who has been working on cancer diagnosis and drug delivery systems since 2004. “More importantly, our invention is the first of its kind that allows drug particles to be directed deep into a tumor in a few milliseconds. They can penetrate a depth of 50 cell layers or more — which is about 200 micrometers, twice the width of a human hair. This helps to ensure that the drugs can reach the cancer cells on the surface and also inside the core of the tumor.” Clinical Associate Professor Chia Sing Joo, a Senior Consultant at the Tan Tock Seng Hospital’s Endoscopy Centre and the Urology & Continence Clinic, was one of the consultants for this study. A trained robotic surgeon experienced in the treatment of prostate, bladder and kidney cancer, Chia says, “For anticancer drugs to achieve their best effectiveness, they need to penetrate into the tumor efficiently in order to reach the cystoplasm of all the cancer cells that are being targeted without affecting the normal cells. “Currently, these can be achieved by means of a direct injection into the tumor or by administering a large dosage of anticancer drugs, which can be painful, expensive, impractical and might have various side effects.” The specialist in Uro-oncology added that if NTU’s technology proves to be viable, clinicians might be able to localize and concentrate the anticancer drugs around a tumor, and introduce the drugs deep into tumor tissues in just a few seconds using a clinical ultrasound system. “If successful, I envisage it can be a good alternative treatment in the future, one which is low cost and yet effective for the treatment of cancers involving solid tumors, as it might minimize the side effects of drugs.” The motivation for this research project is to find alternative solutions for drug delivery systems that are non-invasive and safe. Ultrasound uses soundwaves with frequencies higher than those heard by the human ear. It is commonly used for medical imaging such as to get diagnostic images. Magnets, which can draw and attract the microbubbles, are already in use in diagnostic machines such the Magnetic Resonance Imaging (MRI). “We are looking at developing novel drug carriers — essentially better ways of delivering drugs with minimum side effects,” explains Ohl, an expert in biophysics who had published previous studies involving drug delivery systems and bubble dynamics. “Most prototype drug delivery systems on the market face three main challenges before they can be commercially successful: they have to be non-invasive, patient-friendly and yet cost-effective. “Using the theory of microbubbles and how their surface vibrates under ultrasound, we were able to come up with our solution that addresses these three challenges.” This study, which took two and a half years, involved a 12-man international interdisciplinary team consisting of NTU scientists as well as scientists from City University of Hong Kong and Technion-Israel Institute of Technology (Technion). Two NTU undergraduates doing their Final Year Project and one student in Summer Research Internship Program (NTU) were also part of the team. Moving forward, the team will be adopting this new drug delivery system in studies on lung and liver cancer using animal models, and eventually clinical studies. They estimate that it will take another eight to 10 years before it reaches human clinical trials. Source: Nanyang Technological University


News Article | September 13, 2016
Site: www.rdmag.com

Researchers in Singapore have developed a new protein that can alter DNA in living cells with much higher precision than current methods. The ability to alter DNA accurately will open more doors in the development of personalised medicine that could help to tackle human diseases that currently have few treatment options. Examples of diseases that have unmet therapeutic needs include neurodegenerative diseases like Huntington's disease, muscular dystrophies, and blood disorders like sickle cell anaemia. This new protein, named iCas, can be easily controlled by an external chemical input and thus solves some of the problems with CRISPR-Cas*, the existing gold-standard for DNA altering. For example, existing Cas enzymes may sometimes alter places in the DNA that result in dire consequences. With iCas, users now have the ability to control enzyme activity and thus minimize unintended DNA modifications in the cell. Developed by a collaboration between A*STAR's Genome Institute of Singapore (GIS) and Nanyang Technological University, Singapore (NTU Singapore), iCas was published in the peer reviewed scientific journal Nature Chemical Biology this week. Leading the joint research team is Dr Tan Meng How, Senior Research Scientist of Stem Cell & Regenerative Biology at the GIS, and Assistant Professor at NTU's School of Chemical and Biomedical Engineering. "DNA is like an instruction manual that tells living cells how to behave, so if we can rewrite the instructions in this manual, we will be able to gain control over what the cells are supposed to do," explained Dr Tan. "Our engineered iCas protein is like a light switch that can be readily turned on and off as desired. It also outperforms other existing methods in terms of response time and reliability." To ensure that DNA is precisely altered, which is required in many biomedical and biotechnological applications, the activity of the Cas protein must be tightly regulated. The chemical that switches the iCas protein on or off is tamoxifen, a drug commonly used to treat and prevent breast cancer. In its absence, iCas is switched off with no changes made to the DNA. When switched on with tamoxifen, iCas will then edit the target DNA site. In the study, iCas was found to outperform other chemical-inducible CRISPR-Cas technologies, with a much faster response time and an ability to be switched on and off repeatedly. The higher speed at which iCas reacts will enable tighter control over exactly where and when DNA editing takes place. This is useful in research or applications that demand precise control of DNA editing. For example, in studies of cell signalling pathways or vertebrate development, iCas can precisely target a subset of cells within a tissue (spatial control) or to edit the DNA at a particular developmental stage (temporal control). "The iCas technology developed by Dr Tan is an exciting addition to the growing CRISPR toolbox. It enables genome editing in a precisely controlled manner, thus opening new doors for applications of the CRISPR technology in basic and applied biological research," said Dr Huimin Zhao, the Steven L. Miller Chair Professor of the Chemical and Biomolecular Engineering faculty at the University of Illinois at Urbana-Champaign (UIUC). GIS Executive Director Prof Ng Huck Hui added, "This development allows the researchers to have precision control for more accurate DNA editing, and it can help researchers engineer cells with new properties or repair diseased cells with mutated DNA." Prof Teoh Swee Hin, Chair of NTU's School of Chemical and Biomedical Engineering, said, "DNA editing is an exciting field with many potential uses in the treatment of diseases. NTU has been active in research in the area of gene sequencing and bioengineering over the past years and this work by Dr Tan and his Singapore team will add to the growing body of knowledge in cell engineering for medicine."

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