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用于癌症超声诊疗的空化诱导介孔二氧化硅-二氧化钛纳米颗粒

Cavitation-Inducible Mesoporous Silica-Titania Nanoparticles for Cancer Sonotheranostics.

作者信息

Lee Jeongjin, Kim Jae-Hyun, You Dong Gil, Kim Sohyun, Um Wooram, Jeon Jueun, Kim Chan Ho, Joo Hyeyeon, Yi Gi-Ra, Park Jae Hyung

机构信息

Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.

School of Chemical Engineering, College of Engineering, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, 16419, Republic of Korea.

出版信息

Adv Healthc Mater. 2020 Oct;9(19):e2000877. doi: 10.1002/adhm.202000877. Epub 2020 Sep 7.

Abstract

Sonodynamic therapy has received increasing attention for cancer treatments as an alternative to photodynamic therapy. However, its clinical applications have been limited by the lack of a sonosensitizer that is capable of producing sufficient amounts of reactive oxygen species (ROS) in response to ultrasound (US) exposure. Herein, PEGylated mesoporous silica-titania nanoparticles (P-MSTNs) are prepared and used as US-responsive nanocarriers for cancer sonotheranostics. Perfluorohexane (PFH), which is chosen as the gas precursor, is physically encapsulated into P-MSTNs using the oil-in-water emulsion method. Owing to the vaporization of the gas precursor, PFH@P-MSTNs (137 nm in diameter) exhibit a strong photoacoustic signal in vivo for at least 6 h. Compared to P-MSTNs, PFH@P-MSTNs generate significantly higher amounts of ROS due to the nanobubble-induced cavitation in the presence of US. When systemically administered to tumor-bearing mice, PFH@P-MSTNs effectively accumulate in the tumor site due to the passive targeting mechanism. Consequently, PFH@P-MSTNs show much higher antitumor efficacy than P-MSTNs due to the enhanced cavitation-mediated ROS generation in response to US exposure. It is considered that PFH@P-MSTNs may hold significant potential for cancer sonotheranostics.

摘要

作为光动力疗法的替代方法,声动力疗法在癌症治疗中受到越来越多的关注。然而,其临床应用受到限制,因为缺乏一种能够在超声(US)照射下产生足够量活性氧(ROS)的声敏剂。在此,制备了聚乙二醇化介孔二氧化硅-二氧化钛纳米颗粒(P-MSTNs),并将其用作癌症声动力治疗诊断的超声响应纳米载体。选择全氟己烷(PFH)作为气体前驱体,采用水包油乳液法将其物理包裹在P-MSTNs中。由于气体前驱体的汽化,PFH@P-MSTNs(直径137 nm)在体内至少6小时内表现出强烈的光声信号。与P-MSTNs相比,在超声存在下,PFH@P-MSTNs由于纳米气泡诱导的空化作用而产生显著更多的ROS。当全身给药于荷瘤小鼠时,PFH@P-MSTNs由于被动靶向机制而有效地在肿瘤部位积累。因此,由于在超声照射下空化介导的ROS生成增强,PFH@P-MSTNs显示出比P-MSTNs更高的抗肿瘤疗效。据认为,PFH@P-MSTNs在癌症声动力治疗诊断方面可能具有巨大潜力。

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