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脂质体包封光化学 NO 前体用于控制一氧化氮释放和同时荧光成像。

Liposome encapsulation of a photochemical NO precursor for controlled nitric oxide release and simultaneous fluorescence imaging.

机构信息

Department of Chemistry and Biochemistry, University of California-Santa Barbara, CA 93106, United States.

出版信息

Mol Pharm. 2012 Oct 1;9(10):2950-5. doi: 10.1021/mp300139y. Epub 2012 Sep 20.

Abstract

Described are photochemical studies of the nitric oxide precursors, trans-Cr(L)(ONO)(2)(+) (L = cyclam = 1,4,8,11-tetraazacyclotetradecane, CrONO, or L = mac = 5,7-dimethyl-6-anthracenylcyclam, mac-CrONO) encapsulated in phosphatidylcholine liposomes. The liposomes provide a means to maintain a localized high concentration of NO releasing complexes and are easily modified for in vivo targeting through self-assembly. Steady, controlled release of NO is seen after photolysis of the liposome-encapsulated CrONO as compared to the burst of NO release seen by the unencapsulated complex in oxygenated solutions. The quantum yields for photochemical NO release from liposome-encapsulated CrONO and mac-CrONO were determined in both oxygenated and anoxic solutions. The quantum yield for NO release in oxygenated solution for encapsulated CrONO was more than 5 times larger than that of unencapsulated CrONO, thus the net NO released after photolysis in oxygenated solutions is enhanced by encapsulation of CrONO in liposomes. Encapsulated mac-CrONO shows NO release after photolysis with low-intensity blue light. Furthermore, the fluorescence of mac-CrONO can be detected through the liposomes, thus allowing for development of theranostic NO delivery vessels where tracking and imaging can occur simultaneously with therapeutic NO release. This work provides insight into the development of multifunctional liposome constructs for disease theranostics.

摘要

描述了一氧化氮前体的光化学研究,反式-Cr(L)(ONO)(2)(+)(L = 环戊二胺= 1,4,8,11-四氮杂环十四烷,CrONO,或 L = mac = 5,7-二甲基-6-蒽基环戊二胺,mac-CrONO)包裹在磷脂酰胆碱脂质体中。脂质体提供了一种维持局部高浓度一氧化氮释放复合物的方法,并且通过自组装很容易修饰用于体内靶向。与未包裹的复合物在含氧溶液中看到的一氧化氮爆发释放相比,光解脂质体包裹的 CrONO 后可以看到稳定、可控的一氧化氮释放。在含氧和缺氧溶液中测定了光解脂质体包裹的 CrONO 和 mac-CrONO 从光化学 NO 释放的量子产率。含氧溶液中包裹的 CrONO 的 NO 释放量子产率比未包裹的 CrONO 大 5 倍以上,因此 CrONO 包裹在脂质体中可以增强光解后在含氧溶液中释放的净一氧化氮。光解后,包裹的 mac-CrONO 可以用低强度蓝光释放一氧化氮。此外,mac-CrONO 的荧光可以通过脂质体检测到,从而允许开发治疗性一氧化氮递药载体,其中跟踪和成像可以与治疗性一氧化氮释放同时发生。这项工作为多功能脂质体构建体用于疾病治疗学的发展提供了深入的了解。

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