Caleosin-based nanoscale oil bodies for targeted delivery of hydrophobic anticancer drugs |
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Authors: | Chung-Jen Chiang Li-Jen Lin Chih-Jung Chen |
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Institution: | (1) Department of Medical Laboratory Science and Biotechnology, China Medical University, 91 Hsue-Shih Road, Taichung, 40402, Taiwan;(2) School of Chinese Medicine, China Medical University, Taichung, Taiwan |
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Abstract: | Nanoscale artificial oil bodies (NOBs) could be assembled from plant oil, phospholipids (PLs), and oleosin (Ole) as previously
reported. NOBs have a lipid-based structure that contains a central oil space enclosed by a monolayer of Ole-bound PLs. As
an oil structural protein, Ole functions to maintain the integrity of NOBs. Like Ole, caleosin (Cal) is a plant oil-associated
protein. In this study, we investigated the feasibility of NOBs assembled by Cal for targeted delivery of drugs. Cal was first
fused with anti-HER2/neu affibody (ZH2), and the resulting fusion gene (Cal–ZH2) was then expressed in Escherichia coli. Consequently, NOBs assembled with the fusion protein were selectively internalized by HER2/neu-positive tumor cells. The internalization efficiency could reach as high as 90%. Furthermore, a hydrophobic anticancer drug,
Camptothecin (CPT), was encapsulated into Cal-based NOBs. These CPT-loaded NOBs had a size around 200 nm and were resistant
to hemolysis. Release of CPT from NOBs at the non-permissive condition followed a sustained and prolonged profile. After administration
of the CPT formulation, Cal–ZH2-displayed NOBs exhibited a strong antitumor activity toward HER2/neu-positive cells both in vitro and in vivo. The result indicates the potential of Cal-based NOBs for targeted delivery of hydrophobic drugs. |
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