Visualization of host-guest interactions driven bioorthogonal homing effects at the single cell level in vivo

The clinical translation of anticancer nanomedicine is highly limited thus far, due to their various nonspecific accumulation and relatively low targeting efficiency in the tumor. Herein, we established a bioorthogonal targeting strategy that relies on high specific, supramolecular recognition between beta-cy-clodextrin-modified tumor cells and adamantane-modified nanomedicine. The host-guest interactions driven targeting process was visualized in vivo at the single-cell level for the first time. In this study, host molecule modified cancer cells were implanted into transparent zebrafish embryos, followed by intravenous injection of guest-molecule modified nanomedicine. Fluorescence micrographs confirmed that the guest-modified liposomes could rapidly adhere onto the surface of host-modified melanoma cells, deliver doxorubicin after internalization, and subsequently induce apoptosis of cancer cells in zebrafish. In addition, host-modified liposomes that were injected shortly after guest-modified liposomes could accumulate in the tumor site together with guest-modified liposomes mediated via host-guest interactions, serving as a secondary drug delivery system. These data provides important, most direct evidence showing the host-guest interactions driven bioorthogonal homing effects in vivo.(c) 2022 Elsevier Ltd. All rights reserved.