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Publication List English
2021/10/31
Generation of a Transgenic Zebrafish Line for In Vivo Assessment of Hepatic Apoptosis
2021/08/19
2021/07/09
Establishment of a Quality Control Protocol for Zebrafish Developmental Toxicity Studies
2020/10/13
2020/05/28
A novel orexin antagonist from a natural plant was discovered using zebrafish behavioural analysis
2019/10/15
C3orf70 Is Involved in Neural and Neurobehavioral Development
2019/09/22
2019/07/17
Aging-associated microstructural deterioration of vertebra in zebrafish
2019/03/18
Zebrafish yolk sac microinjection of thalidomide for assessment of developmental toxicology
2019/02/18
Toxicological Evaluation of SiO2 Nanoparticles by Zebrafish Embryo Toxicity Test
Application of Coiled Coil Peptides in Liposomal Anti-Cancer Drug Delivery Using a Zebrafish Xenograft Model.
2016/12/17
ACS Nano. 2016;10:7428-7435
Yang J, Shimada Y, Olsthoorn RC, Snaar-Jagalska BE, Spaink HP, Kros A.
The complementary coiled coil forming peptides E4 [(EIAALEK)4] and K4 [(KIAALKE)4] are known to trigger liposomal membrane fusion when tethered to lipid vesicles in the form of lipopeptides. In this study, we examined whether these coiled coil forming peptides can be used for drug delivery applications. First, we prepared E4 peptide modified liposomes containing the far-red fluorescent dye TO-PRO-3 iodide (E4-Lipo-TP3) and confirmed that E4-liposomes could deliver TP3 into HeLa cells expressing K4 peptide on the membrane (HeLa-K) under cell culture conditions in a selective manner. Next, we prepared doxorubicin-containing E4-liposomes (E4-Lipo-DOX) and confirmed that E4-liposomes could also deliver DOX into HeLa-K cells. Moreover, E4-Lipo-DOX showed enhanced cytotoxicity toward HeLa-K cells compared to free doxorubicin. To prove the suitability of E4/K4 coiled coil formation for in vivo drug delivery, we injected E4-Lipo-TP3 or E4-Lipo-DOX into zebrafish xenografts of HeLa-K. As a result, E4-liposomes delivered TP3 to the implanted HeLa-K cells, and E4-Lipo-DOX could suppress cancer proliferation in the xenograft when compared to nontargeted conditions (i.e., zebrafish xenograft with free DOX injection). These data demonstrate that coiled coil formation enables drug selectivity and efficacy in vivo. It is envisaged that these findings are a step forward toward biorthogonal targeting systems as a tool for clinical drug delivery.
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