Light-Triggered Cancer Cell Specific Targeting and Liposomal Drug Delivery in a Zebrafish Xenograft Model

Cell-specific drug delivery remains a major unmet challenge for cancer nanomedicines. Here, light-triggered, cell-specific delivery of liposome-encapsulated doxorubicin to xenograft human cancer cells in live zebrafish embryos is demonstrated. This method relies on light-triggered dePEGylation of liposome surfaces to reveal underlying targeting functionality. To demonstrate general applicability of this method, light-triggered, MDA-MB-231 breast cancer cell specific targeting in vivo (embryonic zebrafish) is shown using both clinically relevant, folate-liposomes, as well as an experimental liposome-cell fusion system. In the case of liposome-cell fusion, the delivery of liposomal doxorubicin direct to the cytosol of target cancer cells results in enhanced cytotoxicity, compared to doxorubicin delivery via either folate-liposomes or free doxorubicin, as well as a significant reduction in xenograft cancer cell burden within the embryonic fish.