> Details

Tansi, Felista Lemnyui [Author]; Rüger, Ronny [Author]; Böhm, Claudia [Author]; Steiniger, Frank [Author]; Raasch, Martin [Author]; Mosig, Alexander S. [Author]; Kontermann, Roland [Author]; Teichgräber, Ulf [Author]; Fahr, Alfred [Author]; Hilger, Ingrid [Author]

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

Reference
management

Bookmarks

Remove from
bookmarks

Share this on Whatsapp

Close

Bookmarks



You can manage bookmarks using lists, please log in to your user account for this.
  • Media type: E-Article
  • Title: 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
  • Contributor: Tansi, Felista Lemnyui [VerfasserIn]; Rüger, Ronny [VerfasserIn]; Böhm, Claudia [VerfasserIn]; Steiniger, Frank [VerfasserIn]; Raasch, Martin [VerfasserIn]; Mosig, Alexander S. [VerfasserIn]; Kontermann, Roland [VerfasserIn]; Teichgräber, Ulf [VerfasserIn]; Fahr, Alfred [VerfasserIn]; Hilger, Ingrid [VerfasserIn]
  • imprint: Oct 15
  • Published in: Pharmaceutics ; (2020,10) Artikel-Nummer 972, 21 Seiten
  • Language: English
  • DOI: 10.3390/pharmaceutics12100972
  • ISSN: 1999-4923
  • Identifier:
  • Origination:
  • Footnote:
  • Description: 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.
  • Access State: Open Access