Rapid Target Binding and Cargo Release of Activatable Liposomes Bearing HER2 and FAP Single-Chain Antibody Fragments Reveal Potentials for Image-Guided Delivery to Tumors / Felista L Tansi, Ronny Rüger, Claudia Böhm, Frank Steiniger, Martin Raasch, Alexander S Mosig, Roland E Kontermann, Ulf K Teichgräber, Alfred Fahr, Ingrid Hilger

Abstract: Liposomes 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.Keywords: HER2; fluorescence quenching; liposomes; molecular targeting; optical imaging; tumor heterogeneity; tumor microenvironment..

Medienart:	E-Artikel

Erscheinungsjahr:	Oct 15 2020
Erschienen:	Oct 15

Enthalten in:	Zur Gesamtaufnahme - volume:12
Enthalten in:	Pharmaceutics - (2020,10) Artikel-Nummer 972, 21 Seiten

Sprache:	Englisch

Beteiligte Personen:	Tansi, Felista Lemnyui, 1974- [VerfasserIn] Rüger, Ronny, 1979- [VerfasserIn] Böhm, Claudia [VerfasserIn] Steiniger, Frank, 1971- [VerfasserIn] Raasch, Martin, 1938-2008 [VerfasserIn] Mosig, Alexander S. [VerfasserIn] Kontermann, Roland, 1961- [VerfasserIn] Teichgräber, Ulf, 1970- [VerfasserIn] Fahr, Alfred, 1949- [VerfasserIn] Hilger, Ingrid, 1963- [VerfasserIn]

Links:	doi.org [kostenfrei]

Umfang:	8 Illustrationen (farbig)

doi:	10.3390/pharmaceutics12100972

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	1736702386