ZFIN ID: ZDB-PUB-160810-4
Application of Coiled Coil Peptides in Liposomal Anti-Cancer Drug Delivery Using a Zebrafish Xenograft Model
Yang, J., Shimada, Y., Olsthoorn, R.C., Snaar-Jagalska, B.E., Spaink, H.P., Kros, A.
The complementary coiled coil forming peptides E [(EIAALEK)4] and K [(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 towards 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 to 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 non-targeted 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 towards biorthogonal targeting systems as a tool for clinical drug delivery.