{"647090":{"#nid":"647090","#data":{"type":"news","title":"Breaching the Blood-Brain Barrier to Deliver Precious Payloads","body":[{"value":"\u003Cp\u003ERNA-based drugs have the potential to change the standard of care for many diseases, making personalized medicine a reality. This rapidly expanding class of therapeutics are cost-effective, fairly easy to manufacture, and able to go where no drug has gone before, reaching previously undruggable pathways.\u003C\/p\u003E\u003Cp\u003EMostly.\u003C\/p\u003E\u003Cp\u003ESo far, these promising drugs haven\u2019t been very useful in getting through to the well-protected brain to treat tumors or other maladies.\u003C\/p\u003E\u003Cp\u003ENow a multi-institutional team of researchers, led by \u003Ca href=\u0022https:\/\/arvanitis.gatech.edu\/\u0022\u003ECostas Arvanitis\u003C\/a\u003E at the Georgia Institute of Technology and Emory University, has figured out a way: using ultrasound and RNA-loaded nanoparticles to get through the protective blood-brain barrier and deliver potent medicine to brain tumors.\u003C\/p\u003E\u003Cp\u003E\u201cWe\u2019re able to make this drug more available to the brain and we\u2019re seeing a substantial increase in tumor cell death, which is huge,\u201d said Arvanitis, assistant professor in the Wallace H, Coulter Department of Biomedical Engineering (BME) and Georgia Tech\u2019s George W. Woodruff School of Mechanical Engineering (ME).\u003C\/p\u003E\u003Cp\u003EArvanitis, whose collaborators include researchers and clinicians from Emory\u2019s School of Medicine and the University of Cincinnati College of Medicine, is the corresponding author of a \u003Ca href=\u0022https:\/\/advances.sciencemag.org\/content\/7\/18\/eabf7390\/tab-article-info\u0022\u003Enew paper\u003C\/a\u003E published in the journal \u003Ca href=\u0022https:\/\/advances.sciencemag.org\/\u0022\u003E\u003Cem\u003EScience Advances\u003C\/em\u003E\u003C\/a\u003E that describes the team\u2019s development of a next-generation, tunable delivery system for RNA-based therapy in brain tumors.\u003C\/p\u003E\u003Cp\u003E\u201cOur results were very positive, but if you think I\u2019m excited, you haven\u2019t talked to oncologists \u2013 they\u2019re 10 times as excited,\u201d Arvanitis said.\u003C\/p\u003E\u003Cp\u003EThe roots of this project go back to when he and the paper\u2019s lead author, ME grad student Yutong Guo, arrived at Georgia Tech in August 2016.\u003C\/p\u003E\u003Cp\u003E\u201cFrom the start, I was very interested in the application of ultrasonics in treating brain disease,\u201d said Arvanitis, who linked up with Emory physician \u003Ca href=\u0022https:\/\/www.pedsresearch.org\/research-group\/macdonald-laboratory\u0022\u003ETobey MacDonald\u003C\/a\u003E, director of the Pediatric Neuro-Oncology Program at the Aflac Cancer and Blood Disorders Center, and one of the paper\u2019s co-authors. \u201cOur main question was, can we use ultrasound to deliver drugs to tumors? Because that is a major challenge.\u201d\u003C\/p\u003E\u003Cp\u003ERNA drugs have two major weaknesses: limited circulation time and limited uptake by cells. To overcome these challenges, the drugs are packaged in robust nanocarriers, typically 100 nm in size, to improve their bioavailability. Still, these nanocarriers have typically been too large to penetrate the blood-brain barrier, the tightly-connected and selective endothelial cells surrounding blood vessels in the brain, until now a locked door to RNA drugs.\u003C\/p\u003E\u003Cp\u003EBut now, Arvanitis and his colleagues have discovered a safe way to get the drug safely across.\u003C\/p\u003E\u003Cp\u003EUsing mouse models, the team deployed a modified version of ultrasound, the diagnostic imaging technique that uses sound waves to create images of internal body structures, such as tendons, blood vessels, organs and, in the case of pregnant women, babies in utero. The researchers combined this technology with microbubbles \u2014 tiny gas pockets in the bloodstream, designed as vascular contrast agents for imaging \u2014 which vibrate in response to ultrasound waves, changing the permeability of blood vessels.\u003C\/p\u003E\u003Cp\u003E\u201cFocusing multiple beams of ultrasound energy onto a cancerous spot caused the microbubbles\u2019 vibrations to actually stretch, pull, or shear the tight junctions of endothelial tissue that make up the blood-brain barrier, creating an opening for drugs to get through,\u201d Guo said.\u003C\/p\u003E\u003Cp\u003EIt\u2019s a technique that biomedical ultrasound researchers have been refining for more than a decade, and recent clinical trials have demonstrated its safety. But there hasn\u2019t been much evidence for selective and effective delivery of nanoparticles and their payloads directly into brain tumor cells. But even when blood borne drugs succeed in penetrating the blood-brain barrier, if they are not taken up by the cancer cell, the job isn\u2019t complete.\u003C\/p\u003E\u003Cp\u003EArvanitis and his team packaged siRNA, a drug that can block the expression of genes that drive tumor growth, in lipid-polymer hybrid nanoparticles, and combined that with the focused ultrasound technique in pediatric and adult preclinical brain cancer models. Using single-cell image analysis, they demonstrated a more than 10-fold improvement in delivery of the drug, reducing harmful protein production and increasing tumor cell death in preclinical models of medulloblastoma, the most common malignant brain tumor in children.\u003C\/p\u003E\u003Cp\u003E\u201cThis is completely tunable,\u201d Arvanitis said. \u201cWe can fine tune the ultrasound pressure to attain a desired level of vibration and by extension drug delivery. It\u2019s non-invasive, because we are applying sound from outside the brain, and it\u2019s very localized, because we can focus the ultrasound to a very small region of the brain.\u201d\u003C\/p\u003E\u003Cp\u003ECurrent standard treatments for brain tumors come with potentially awful side effects, Arvanitis said, \u201chowever, this technology can provide treatment with minimal side effects, which is very exciting. Now we are moving forward to try and identify what components are missing to translate this technology to the clinic.\u201d\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ECitation:\u003C\/strong\u003E Y. Guo, H. Lee,\u0026nbsp;Z. Fang, A. Velalopoulou, J. Kim,\u0026nbsp;B. Thomas, T. Kim,\u0026nbsp;A. F. Coskun,\u0026nbsp;D. P. Krummel, S. Sengupta, T. McDannold, and C. D. Arvanitis.\u0026nbsp;\u201cSingle-cell analysis reveals effective siRNA delivery in brain tumors with microbubble-enhanced ultrasound and cationic nanoparticles\u201d\u0026nbsp;\u003Cem\u003EScience Advances,\u003C\/em\u003E\u0026nbsp;April 2021.\u003C\/p\u003E\u003Cp\u003E\u003Cem\u003EThis work was supported by the National Institutes of Health (NIH), grant No. R00 EB016971 and grant No. R37 CA239039; and the CURE Foundation.\u003C\/em\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ERelated Links\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003E\u003Ca href=\u0022https:\/\/arvanitis.gatech.edu\/\u0022\u003EArvanitis Lab\u003C\/a\u003E\u003C\/p\u003E\u003Cp\u003E\u003Ca href=\u0022https:\/\/advances.sciencemag.org\/content\/7\/18\/eabf7390\/tab-article-info\u0022\u003E\u201cSingle-cell analysis reveals effective siRNA delivery in brain tumors with microbubble-enhanced ultrasound and cationic nanoparticles\u201d\u003C\/a\u003E\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E","summary":"","format":"limited_html"}],"field_subtitle":[{"value":"Georgia Tech and Emory researchers use ultrasound to develop delivery system for potent RNA drugs"}],"field_summary":[{"value":"\u003Cp\u003EResearchers at Georgia Tech and Emory University have developed a method using ultrasound and RNA-loaded nanoparticles to penetrate the blood-brain barrier, offering a promising new approach for treating brain tumors.\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"Georgia Tech and Emory researchers use ultrasound to develop delivery system for potent RNA drugs"}],"uid":"28153","created_gmt":"2021-04-30 20:40:24","changed_gmt":"2024-09-26 19:18:52","author":"Jerry Grillo","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2021-04-30T00:00:00-04:00","iso_date":"2021-04-30T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"647088":{"id":"647088","type":"image","title":"Yutong and Costas","body":null,"created":"1619810931","gmt_created":"2021-04-30 19:28:51","changed":"1619810931","gmt_changed":"2021-04-30 19:28:51","alt":"","file":{"fid":"245668","name":"Costas and Yutong.jpg","image_path":"\/sites\/default\/files\/images\/Costas%20and%20Yutong.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/Costas%20and%20Yutong.jpg","mime":"image\/jpeg","size":1902092,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/Costas%20and%20Yutong.jpg?itok=2EeTXQKc"}}},"media_ids":["647088"],"groups":[{"id":"1292","name":"Parker H. Petit Institute for Bioengineering and Bioscience (IBB)"},{"id":"1188","name":"Research Horizons"}],"categories":[],"keywords":[{"id":"1612","name":"BME"},{"id":"187715","name":"brain disease"},{"id":"385","name":"cancer"},{"id":"147731","name":"brain tumors"},{"id":"187716","name":"RNA therapeutics"},{"id":"187717","name":"RNA drugs"},{"id":"2973","name":"nanoparticles"},{"id":"187718","name":"nanocarriers"},{"id":"187915","name":"go-researchnews"},{"id":"187423","name":"go-bio"}],"core_research_areas":[{"id":"39441","name":"Bioengineering and Bioscience"}],"news_room_topics":[{"id":"71891","name":"Health and Medicine"}],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003EWriter: Jerry Grillo\u003C\/p\u003E","format":"limited_html"}],"email":["Jerry.grillo@ibb.gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}