Liposome Encapsulation of a Photochemical NO Precursor for Controlled Nitric Oxide Release and Simultaneous Fluorescence Imaging

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.