Ultrasound-mediated drug-free theranostics for treatment of prostate cancer  

作　　者：Reshani Himashika Perera Felipe Matias Berg Eric Chua Abenojar Pinunta Nittayacharn Youjoung Kim Xinning Wang James Peter Basilion Agata Exner 

机构地区：[1]Department of Radiology,Case Western Reserve University,Cleveland,OH,44106,USA [2]Hospital Israelita Albert Einstein,S˜ao Paulo,SP,05652-900,Brazil [3]Department of Biomedical Engineering,Faculty of Engineering,Mahidol University,Puttamonthon,Nakorn Pathom,73170,Thailand [4]Department of Biomedical Engineering,Case Western Reserve University,Cleveland,44106,OH,USA

出　　处：《Bioactive Materials》2024年第5期45-55,共11页生物活性材料（英文）

基　　金：Felipe Berg is supported by the Marcos Lottenberg&Marcus Wolosker International Fellowship for Physician-Scientist Training Program;We acknowledge the support from Siemens Healthineers for providing the ultrasound device for the rabbit studies and the funding source of this study:National Institute of Biomedical Imaging and Bioengineering(NIBIB)(Award No.5R01-EB025741);the Case-Coulter Translational Research Partnership/Wallace H.Coulter Foundation.

摘　　要：Lipid-shelled nanobubbles(NBs)can be visualized and activated using noninvasive ultrasound(US)stimulation,leading to significant bioeffects.Prior work demonstrates that active targeting of NBs to prostate-specific membrane antigen(PSMA)overexpressed in prostate cancer(PCa)results in enhanced cellular internalization and prolongs NB retention with persistent,cancer-cell specific acoustic activity.In this work,we hypothesized that tumor-accumulated PSMA-NBs combined with low frequency unfocused therapeutic US(TUS)will lead to selective damage and induce a specific therapeutic effect in PSMA-expressing tumors compared to PSMA-negative tumors.We observed that the internalized NBs and cellular compartments were disrupted after the PSMA-NB+TUS(targeted NB therapy or TNT)application,yet treated cells remained intact and viable.In vivo,PSMA-expressing tumors in mice receiving TNT treatment demonstrated a significantly greater extent of apoptosis(78.4±9.3%,p<0.01)compared to controls.TNT treatment significantly inhibited the PSMA expressing tumor growth and increased median survival time by 103%,p<0.001).A significant reduction in tumor progression compared to untreated control was also seen in an orthotopic rabbit PCa model.Results demonstrate that cavitation of PSMA-NBs internalized via receptor-mediated endocytosis into target PCa cells using unfocused ultrasound results in significant,tumor-specific bioeffects.The effects,while not lethal to PSMA-expressing cancer cells in vitro,result in significant in vivo reduction in tumor progression in two models of PCa.While the mechanism of action of these effects is yet unclear,it is likely related to a locally-induced immune response,opening the door to future investigations in this area.

关 键 词：NANOBUBBLES PC-3 Cells Contrast enhanced ultrasound Prostate-specific membrane antigen(PSMA) Ultrasound-mediated therapy 

分 类 号：R737.25[医药卫生—肿瘤]