ICUS Weekly News Monitor 12-16-2016

1.  Theranostics,  Jan 1, 2017,  Efficient Enhancement of Blood-Brain Barrier Permeability Using Acoustic Cluster Therapy (ACT)
Authors:  Andreas K.O. Åslund, et al
2.  Oncotarget,  Dec 14, 2016,  Biodegradable double-targeted PTX-mPEG-PLGA nanoparticles for ultrasound contrast enhanced imaging and antitumor therapy in vitro     Authors:  Jing Ma, et al.
3.,  Dec 14, 2016,  IQ4I Research & Consultancy Published a New Report on “Ultrasound medical devices Global Market – Forecast To 2023”
Author: Monika Donimirska
4.,  Dec 12, 2016,  Nanomedical treatment concept combines NO gas therapy with starvation of tumor cells

Theranostics 2017; 7(1):23-30. doi:10.7150/thno.16577
Jan 1, 2017
Efficient Enhancement of Blood-Brain Barrier Permeability Using Acoustic Cluster Therapy (ACT)
Authors:  Andreas K.O. Åslund1 Corresponding address, Sofie Snipstad1, Andrew Healey2, Svein Kvåle2, Sverre H. Torp3,4, Per C. Sontum2, Catharina de Lange Davies1, Annemieke van Wamel1
1. Department of Physics, Norwegian University of Science and Technology (NTNU), Trondheim, Norway;
2. Phoenix Solutions AS, Oslo, Norway;
3. Department of Pathology and Medical Genetics, St. Olavs University Hospital, Trondheim, Norway;
4. Department of Laboratory Medicine, Children's and Women's Health, NTNU, Trondheim, Norway.
The blood-brain barrier (BBB) is a major obstacle in drug delivery for diseases of the brain, and today there is no standardized route to surpass it. One technique to locally and transiently disrupt the BBB, is focused ultrasound in combination with gas-filled microbubbles. However, the microbubbles used are typically developed for ultrasound imaging, not BBB disruption. Here we describe efficient opening of the BBB using the promising novel Acoustic Cluster Therapy (ACT), that recently has been used in combination with Abraxane® to successfully treat subcutaneous tumors of human prostate adenocarcinoma in mice. ACT is based on the conjugation of microbubbles to liquid oil microdroplets through electrostatic interactions. Upon activation in an ultrasound field, the microdroplet phase transfers to form a larger bubble that transiently lodges in the microvasculature. Further insonation induces volume oscillations of the activated bubble, which in turn induce biomechanical effects that increase the permeability of the BBB. ACT was able to safely and temporarily permeabilize the BBB, using an acoustic power 5-10 times lower than applied for conventional microbubbles, and successfully deliver small and large molecules into the brain.
DOI: 10.18632/oncotarget.13243
Dec 14, 2016
Biodegradable double-targeted PTX-mPEG-PLGA nanoparticles for ultrasound contrast enhanced imaging and antitumor therapy in vitro
Authors:  Jing Ma1,2,3,*, Ming Shen4,*, Chang Song Xu5,*, Ying Sun4, You Rong Duan4, Lian Fang Du2
1Department of Ultrasound, Songjiang Hospital Affiliated to The First People’s Hospital of Shanghai Jiao tong University, Shanghai 201600, China
2Department of Ultrasound, Shanghai First People’s Hospital Affiliated to Shanghai Jiao tong University School of Medicine, Shanghai 200080, China
3Department of Ultrasound, Shanghai East Hospital Affiliated to Tong ji University, Shanghai 200120, China
4State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, P. R. China
5Huai’an First People’s Hospital, Nanjing Medical University, Jiangsu 223001, China
*These authors have contributed equally to this work
Correspondence to:
Lian Fang Du, email: This email address is being protected from spambots. You need JavaScript enabled to view it.
You Rong Duan, email: This email address is being protected from spambots. You need JavaScript enabled to view it.
A porous-structure nano-scale ultrasound contrast agent (UCA) was made of monomethoxypoly (ethylene glycol)-poly (lactic-co-glycolic acid) (mPEG-PLGA), and modified by double-targeted antibody: anti-carcinoembryonic antigen (CEA) and anti-carbohydrate antigen 19-9 (CA19-9), as a double-targeted nanoparticles (NPs). Anti-tumor drug paclitaxel (PTX) was encapsulated in the double-targeted nanoparticles (NPs). The morphor and release curve were characterized. We verified a certain anticancer effect of PTX-NPs through cytotoxicity experiments. The cell uptake result showed much more NPs may be facilitated to ingress the cells or tissues with ultrasound (US) or ultrasound targeted microbubble destruction (UTMD) transient sonoporation in vitro. Ultrasound contrast-enhanced images in vitro and in vivo were investigated. Compared with SonoVue, the NPs prolonged imaging time in rabbit kidneys and tumor of nude mice, which make it possible to further enhance anti-tumor effects by extending retention time in the tumor region. The novel double-targeted NPs with the function of ultrasound contrast enhanced imaging and anti-tumor therapy can be a promising way in clinic.
Dec 14, 2016
IQ4I Research & Consultancy Published a New Report on “Ultrasound medical devices Global Market – Forecast To 2023”
Author: Monika Donimirska
Ultrasound is a kind of imaging technique/procedure that makes use of high-frequency sound waves for scanning and creating an image of body part. Due to its less cost, best imaging quality, workflow efficiency, reliability, no requirement of same computing power, fast frame rates or specialized transducers now-a-days ultrasound scans are most popularly used diagnostic imaging technique.
Boston, MA, December 14, 2016 –(– Ultrasound is one of the renowned technologies in the medical field. This safe, non-invasive and non-use of ionizing radiation procedure involves sound waves of higher frequencies waves, (greater than 20,000 Hz) for producing various structural echo patterns of internal body parts. An ultrasound machine during diagnosis, works by bouncing off sound waves when in contact with solid parts of the body. In addition with the diagnosis, ultrasounds are being used to treat medical conditions too and thereby ultrasounds have role to play in therapeutic application. As estimated by IQ4I Research, Ultrasound medical devices global market is expected to grow at a double digit CAGR to reach $10,106 million by 2023.
Rising population of chronic and lifestyle disorder, availability of public-private investments, increasing demand for point of care testing and rising adoption of ultrasound technology in the various fields especially in cardiology, oncology and emergency medicine are the factors driving the market growth. However, some of the factors like lack of skilled professionals, high cost ultrasound devices, stringent regulations and unfavorable reimbursement cuts may hinder the growth of global ultrasound device market.
Advancements and newer technologies like contrast enhanced ultrasound and ultrasound elastography are revolutionizing ultrasound market. Contrast enhanced ultrasound technology which involves microbubble contrast agents and specialized techniques for imaging the blood flow and perfusion within the human body are becoming most popular medical imaging method. In September 7th, 2016 Toshiba America Medical Systems, Inc. announced its launch of Aplio 500 Platinum contrast enhanced ultrasound system after the recent approval from FDA for the use of microbubbles. Lumason and SonoVue from Bracco Diagnostics, Inc. (U.S.), Optison from GE Healthcare (U.S) are few FDA approved contrast enhanced ultrasound agents. Siemens Healthcare provides Cadence Contrast Pulse Sequencing (CPS) Technology on its ACUSON Sequoia Ultrasound platform providing detailed images of micro and macro vascularity enhancing lesion characterization. Philips HD11 XE has the versatility to expand into a complete digital imaging technology incorporating contrast imaging to enhance cardiovascular imaging capabilities. Similarly Ultrasound elastography is one of the emerging technologies where stress is applied on the organs to assess the mechanical properties (elasticity) and stiffness of fibrotic and cancerous lesions. Hitachi Medical Corporation has developed Real-Time Tissue Elastography (RTTE) application on its Hi Vision Avius ultrasound platform which differentiates the healthy and malignant tissues of breast, thyroid, prostrate, liver and pancreas. In addition the major players such as Toshiba Medical systems introduced elastography technique in its Aplio MX platform, Philips Healthcare on its iU22 platform and Siemens Healthcare in its ACUSON S2000 ultrasound platform.
The ultrasound medical devices global market is segmented based on their technology, display, portability, application, end users and geography. The market by technology is divided into diagnostic and therapeutic, based on display the market is segmented into black & white and color and based on portability market is divided into trolley/cart based and portable ultrasound medical devices. The ultrasound medical devices application is further sub-segmented into radiology/general imaging, women’s health, cardiology, point of care, urology, orthopedic, cancer, neurology and others. The radiology/general imaging occupied highest market in ultrasound medical devices application market.
Geographically, European regions held the largest market share where Germany accounted for the largest share, this growth is driven due to its high acceptance of advanced technologies and sophisticated universal treatment facilities. Among North American regions U.S. dominates, the market with the share of 77.9% and is expected to show a strong growth due to the high advanced healthcare facilities, increased growing awareness about the technological advancements, availability of Medicare and third party insurance facilities, easy availability of skilled personnel are driving the market growth. In Asia- Pacific region, Japan has held the largest market share due to its increase in healthcare spending and advancements in healthcare facilities, the easy access to advanced healthcare technology. In RoW regions, Brazil has the largest market share and is expected to grow at the strong rate due to increasing trends of medical tourism, large patient pool, Medicare facilities and increase in technological advancements.
Some of the prominent players in ultrasound medical device market include Analogic Corporation (U.S), Esaote (Italy), Fujifilm Holdings Corporation (Japan), GE Healthcare (U.S.), Hitachi Ltd (Japan), Koninklijke Philips N.V. (Netherlands), Mindray Medical International Limited (China), Samsung Electronics Co. Ltd (South Korea), Siemens AG (Germany) and Toshiba Medical Systems Corporation (Japan).
Dec 12, 2016
Nanomedical treatment concept combines NO gas therapy with starvation of tumor cells
Read more at:
Biocompatible nanocapsules, loaded with an amino acid and equipped with an enzyme now combine two anti-tumor strategies into a synergistic treatment concept. Researchers hope this increases effectiveness and decreases side effects. In the journal Angewandte Chemie, the scientists explain the concept: tumor cells are deprived of their nutrient glucose as this is converted to toxic nitrogen monoxide (NO) and hydrogen peroxide (H2O2).
NO is a toxic gas that causes smog. However, in low concentrations in the body it is an important messenger molecule that regulates such things as circulation and libido. It is also an important physiological defense weapon against fungi and bacteria. In higher concentrations, NO is capable of killing tumor cells and increasing the effectiveness of photodynamic and radiological treatments. For clinical use, NO needs to be released in the target area from a biocompatible precursor.
The natural amino acid L-arginine (L-Arg) may be useful in such a system, because the native enzyme inducible NO synthase (iNOS) makes NO from L-Arg. NO is also formed when L-Arg is oxidized by H2O2. This is interesting because the microenvironment around tumors is rich in H2O2. This approach to NO gas therapy is being pursued by researchers at Shenzhen University (China), the National Institutes of Health (Bethesda, USA), and the University of Maryland (College Park, USA). Their special twist is to combine this gas therapy with a method for starving cancer cells in a synergistic treatment.
Instead of starving a tumor by blocking the blood vessels that feed it, the researchers intend to remove the glucose that the tumor needs for nutrition by consuming it in a metabolic reaction: the enzyme glucose oxidase (GOx) converts the glucose into gluconic acid and H2O2. The increased H2O2 concentration is a useful side effect, because H2O2 is both cytotoxic and accelerates the release of NO from L-Arg. Another useful side effect is that H2O2 and NO react to form highly toxic peroxynitrites that damage the tumor cells.
The research team led by Peng Huang, Tianfu Wang, and Xiaoyuan Chen has now reached an important milestone in the development of this concept. They have developed biocompatible, biodegradable, porous nanocapsules made of organosilicates that transport GOx and L-Arg into tumor cells simultaneously. GOx is bound to the surface; L-Arg is stored inside the capsule. While the GOx is active immediately after injection of the nanocapsules into the tumor, L-Arg is released little by little, first through the capsule pores, then as the capsule disintegrates. Their large cavity also allows the capsules to serve as an ultrasound contrast material for better localization of the tumor.
Experiments with both cell cultures and mice have demonstrated the significant synergistic effect of this combination therapy, which successfully inhibits cell growth, initiates cell death, and shrinks the tumors in mice.

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