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Targeted PERK inhibition with biomimetic nanoclusters confers preventative and interventional benefits to elastase-induced abdominal aortic aneurysms

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Bioactive Materials 2023年第8期26卷 52-63页

作者： Nisakorn Yodsanit Takuro Shirasu Yitao Huang Li Yin Zain Husain Islam Alexander Christopher Gregg Alessandra Marie Riccio Runze Tang Eric William Kent Yuyuan Wang Ruosen Xie Yi Zhao Mingzhou Ye Jingcheng Zhu Yi Huang Nicholas Hoyt Mengxue Zhang john a.hossack Morgan Salmon K.Craig Kent Lian-Wang Guo Shaoqin Gong Bowen Wang Department of Biomedical Engineering Wisconsin Institute for DiscoveryUniversity of Wisconsin-MadisonMadisonWI53715USA Department of Ophthalmology and Visual Sciences University of Wisconsin-MadisonMadisonWI53715USA Department of Surgery School of MedicineUniversity of VirginiaCharlottesvilleVA22908USA The Biomedical Sciences Graduate Program(BIMS) School of MedicineUniversity of VirginiaCharlottesvilleVA22908USA Department of Biomedical Engineering School of EngineeringUniversity of VirginiaCharlottesvilleVA22908USA School of Medicine and Health Sciences George Washington UniversityWashingtonDC20052USA Department of Cardiac Surgery Michigan MedicineUniversity of MichiganAnn ArborMI48109USA

Abdominal aortic aneurysm(AAA)is a progressive aortic dilatation,causing~80%mortality upon ***,there is no approved drug therapy for *** repairs are invasive and risky and thus not recommended to patients with small AAAs which,however,account for~90%of the newly diagnosed *** is therefore a compelling unmet clinical need to discover effective non-invasive strategies to prevent or slow down AAA *** contend that the first AAA drug therapy will only arise through discoveries of both effective drug targets and innovative delivery *** is substantial evidence that degenerative smooth muscle cells(SMCs)orchestrate AAA pathogenesis and *** this study,we made an exciting finding that PERK,the endoplasmic reticulum(ER)stress Protein Kinase R-like ER Kinase,is a potent driver of SMC degeneration and hence a potential therapeutic ***,local knockdown of PERK in elastase-challenged aorta significantly attenuated AAA lesions in *** parallel,we also conceived a biomimetic nanocluster(NC)design uniquely tailored to AAA-targeting drug *** NC demonstrated excellent AAA homing via a platelet-derived biomembrane coating;and when loaded with a selective PERK inhibitor(PERKi,GSK2656157),the NC therapy conferred remarkable benefits in both preventing aneurysm development and halting the progression of pre-existing aneurysmal lesions in two distinct rodent models of *** summary,our current study not only establishes a new intervention target for mitigating SMC degeneration and aneurysmal pathogenesis,but also provides a powerful tool to facilitate the development of effective drug therapy of AAA.

关键词： Abdominal aortic aneurysm ER stress PERK Biomimetic nanomedicine Targeted delivery

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Intra-Vascular Ultrasound（IVUS）Delivery of DNA Via Microbubble Carriers to an Injured Artery In vivo

Intra-Vascular Ultrasound（IVUS）Delivery of DNA Via Microbu...

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2008 IEEE International Ultrasonics Symposium

作者： Linsey C.Phillips Alexander L.Klibanov Doug K.Bowles Brian.R.Wamhoff john a.hossack University of Virginia.Charlottesville.VA University of Missouri Columbia.MO University of Virginia CharlottesvilleVA

＜正＞Background,Motivation and Objective The most common therapy for narrowed,atherosclerotic arteries is balloon angioplasty and is often followed by stent *** procedure causes injury to the vessel wall and over tim...

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