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
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Pharmaceutics - 12(2020), 10 vom: 15. Okt. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tansi, Felista L [VerfasserIn] |
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| Links: |
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| Themen: |
Fluorescence quenching |
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| Anmerkungen: |
Date Revised 10.11.2020 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3390/pharmaceutics12100972 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM316456268 |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a HER2 | |
| 650 | 4 | |a fluorescence quenching | |
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| 650 | 4 | |a molecular targeting | |
| 650 | 4 | |a optical imaging | |
| 650 | 4 | |a tumor heterogeneity | |
| 650 | 4 | |a tumor microenvironment | |
| 700 | 1 | |a Rüger, Ronny |e verfasserin |4 aut | |
| 700 | 1 | |a Böhm, Claudia |e verfasserin |4 aut | |
| 700 | 1 | |a Steiniger, Frank |e verfasserin |4 aut | |
| 700 | 1 | |a Raasch, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Mosig, Alexander S |e verfasserin |4 aut | |
| 700 | 1 | |a Kontermann, Roland E |e verfasserin |4 aut | |
| 700 | 1 | |a Teichgräber, Ulf K |e verfasserin |4 aut | |
| 700 | 1 | |a Fahr, Alfred |e verfasserin |4 aut | |
| 700 | 1 | |a Hilger, Ingrid |e verfasserin |4 aut | |
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