Theranostic liposomes loaded with quantum dots and apomorphine for brain targeting and bioimaging
Chih-Jen Wen1,*, Li-Wen Zhang2,*, Saleh A Al-Suwayeh3, Tzu-Chen Yen1, Jia-You Fang2,4
1Molecular Imaging Center, Chang Gung Memorial Hospital, Gueishan, Taoyuan, Taiwan; 2Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Gueishan, Taoyuan, Taiwan; 3Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 4Department of Cosmetic Science, Chang Gung University of Science and Technology, Gueishan, Taoyuan, Taiwan
*These authors contributed equally to this work
Abstract: Quantum dots (QDs) and apomorphine were incorporated into liposomes to eliminate uptake by the liver and enhance brain targeting. We describe the preparation, physicochemical characterization, in vivo bioimaging, and brain endothelial cell uptake of the theranostic liposomes. QDs and the drug were mainly located in the bilayer membrane and inner core of the liposomes, respectively. Spherical vesicles with a mean diameter of ~140 nm were formed. QDs were completely encapsulated by the vesicles. Nearly 80% encapsulation percentage was achieved for apomorphine. A greater fluorescence intensity was observed in mouse brains treated with liposomes compared to free QDs. This result was further confirmed by ex vivo imaging of the organs. QD uptake by the heart and liver was reduced by liposomal incorporation. Apomorphine accumulation in the brain increased by 2.4-fold after this incorporation. According to a hyperspectral imaging analysis, multifunctional liposomes but not the aqueous solution carried QDs into the brain. Liposomes were observed to have been efficiently endocytosed into bEND3 cells. The mechanisms involved in the cellular uptake were clathrin- and caveola-mediated endocytosis, which were energy-dependent. To the best of our knowledge, our group is the first to develop liposomes with a QD-drug hybrid for the aim of imaging and treating brain disorders.
Keywords: liposomes, quantum dots, apomorphine, brain targeting, bioimaging
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