Tansi, Felista L.Rüger, RonnyBöhm, ClaudiaSteiniger, FrankRaasch, MartinMosig, Alexander S.Kontermann, Roland E.Teichgräber, Ulf K.Fahr, AlfredHilger, Ingrid2024-04-042024-04-0420201999-49231885614179http://nbn-resolving.de/urn:nbn:de:bsz:93-opus-ds-141922http://elib.uni-stuttgart.de/handle/11682/14192http://dx.doi.org/10.18419/opus-14173Liposomes represent suitable tools for the diagnosis and treatment of a variety of diseases, including cancers. To study the role of the human epidermal growth factor receptor 2 (HER2) as target in cancer imaging and image-guided deliveries, liposomes were encapsulated with an intrinsically quenched concentration of a near-infrared fluorescent dye in their aqueous interior. This resulted in quenched liposomes (termed LipQ), that were fluorescent exclusively upon degradation, dye release, and activation. The liposomes carried an always-on green fluorescent phospholipid in the lipid layer to enable tracking of intact liposomes. Additionally, they were functionalized with single-chain antibody fragments directed to fibroblast activation protein (FAP), a marker of stromal fibroblasts of most epithelial cancers, and to HER2, whose overexpression in 20-30% of all breast cancers and many other cancer types is associated with a poor treatment outcome and relapse. We show that both monospecific (HER2-IL) and bispecific (Bi-FAP/HER2-IL) formulations are quenched and undergo HER2-dependent rapid uptake and cargo release in cultured target cells and tumor models in mice. Thereby, tumor fluorescence was retained in whole-body NIRF imaging for 32-48 h post-injection. Opposed to cell culture studies, Bi-FAP/HER2-IL-based live confocal microscopy of a high HER2-expressing tumor revealed nuclear delivery of the encapsulated dye. Thus, the liposomes have potentials for image-guided nuclear delivery of therapeutics, and also for intraoperative delineation of tumors, metastasis, and tumor margins.eninfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/4.0/570610article2023-11-14