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Targeting RAGE with Nanobodies for Molecular Imaging of Cancers and Alzheimer's Disease
Guangfeng Liang1, Fujing Wang2,3, Wei Xiong2,4,5
1Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, 518118, China.
Abstract:
The receptor for advanced glycation end products (RAGE) is a multifunctional cell surface receptor implicated in aging and the progression of chronic diseases, including cancer and Alzheimer's disease. Its interaction with advanced glycation end products (AGEs) promotes cellular stress and inflammation, underscoring the diagnostic and therapeutic relevance of targeting RAGE. In this study, we explored the potential of nanobodiessingle-domain antibodies known for high specificity, strong affinity, and deep tissue penetrationas molecular tools for RAGE-targeted applications. Using a phage display library, a panel of RAGE-specific nanobodies were isolated and characterized. Binding activity and affinity were evaluated through enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) assays. Among them, nanobody NbF8 demonstrated the highest affinity and specificity toward RAGE. In vitro, NbF8 selectively bound RAGE-expressing cells, while in vivo imaging in renal carcinoma and Alzheimer's disease mouse models confirmed its targeted accumulation in RAGE-overexpressing tumors and brain tissues. These findings highlight NbF8 as a promising molecular imaging agent for RAGE-associated diseases. This study supports the potential of RAGE-targeting nanobodies in both diagnostic imaging and therapeutic development, offering a novel approach for precision medicine in conditions driven by RAGE signaling.
Insights
Researchers developed a novel nanobody, NbF8, targeting the receptor for advanced glycation end products (RAGE). This nanobody shows promise for molecular imaging in diseases like cancer and Alzheimer's, advancing precision medicine.
Area of Science:
- Biotechnology
- Molecular Biology
- Immunology
Background:
- The receptor for advanced glycation end products (RAGE) is a key factor in aging and chronic diseases like cancer and Alzheimer's.
- RAGE's role in cellular stress and inflammation highlights its significance for diagnostics and therapeutics.
- Nanobodies, single-domain antibodies, offer high specificity, affinity, and tissue penetration for targeted applications.
Purpose of the Study:
- To explore nanobodies as molecular tools for RAGE-targeted applications.
- To isolate and characterize RAGE-specific nanobodies.
- To evaluate the diagnostic and therapeutic potential of RAGE-targeting nanobodies.
Main Methods:
- Phage display library was used to isolate RAGE-specific nanobodies.
- Enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) were employed for characterization.
- In vitro cell binding assays and in vivo imaging in mouse models were conducted.
Main Results:
- A panel of RAGE-specific nanobodies was successfully isolated and characterized.
- Nanobody NbF8 exhibited the highest affinity and specificity for RAGE.
- NbF8 demonstrated selective binding to RAGE-expressing cells and targeted accumulation in RAGE-overexpressing tumors and brain tissues in vivo.
Conclusions:
- NbF8 is a promising molecular imaging agent for RAGE-associated diseases.
- RAGE-targeting nanobodies hold potential for diagnostic imaging and therapeutic development.
- This research offers a novel approach for precision medicine in RAGE-driven conditions.
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