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FGF1-gold nanoparticle conjugates targeting FGFR efficiently decrease cell viability upon NIR irradiation
Anna Szlachcic1, Katarzyna Pala, Malgorzata Zakrzewska
1Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Poland.
Abstract:
Fibroblast growth factor receptors (FGFRs) are overexpressed in a wide variety of tumors, such as breast, bladder, and prostate cancer, and therefore they are attractive targets for different types of anticancer therapies. In this study, we designed, constructed, and characterized FGFR-targeted gold nanoconjugates suitable for infrared-induced thermal ablation (localized heating leading to cancer cell death) based on gold nanoparticles (AuNPs). We showed that a recombinant ligand of all FGFRs, human fibroblast growth factor 1 (FGF1), can be used as an agent targeting covalently bound AuNPs to cancer cells overexpressing FGFRs. To assure thermal stability, protease resistance, and prolonged half-life of the targeting protein, we employed highly stable FGF1 variant that retains the biological activities of the wild type FGF1. Novel FGF1 variant, AuNP conjugates are specifically internalized only by the cells expressing FGFRs, and they significantly reduce their viability after irradiation with near-infrared light (down to 40% of control cell viability), whereas the proliferation potential of cells lacking FGFRs is not affected. These results demonstrate the feasibility of FGF1-coated AuNPs for targeted cancer therapy.
Insights
Fibroblast growth factor receptor (FGFR)-targeted gold nanoconjugates show promise for cancer therapy. These novel conjugates utilize a stable FGF1 variant to target cancer cells, leading to significant cell death upon near-infrared light irradiation.
Area of Science:
- Nanotechnology
- Oncology
- Bioconjugation
Background:
- Fibroblast growth factor receptors (FGFRs) are frequently overexpressed in various cancers, including breast, bladder, and prostate cancer.
- This overexpression makes FGFRs attractive targets for developing novel anticancer therapies.
- Targeted therapies aim to selectively deliver therapeutic agents to cancer cells, minimizing damage to healthy tissues.
Purpose of the Study:
- To design, construct, and characterize gold nanoconjugates (AuNPs) targeted to FGFRs for infrared-induced thermal ablation.
- To evaluate the efficacy of these nanoconjugates in selectively targeting and eliminating cancer cells overexpressing FGFRs.
Main Methods:
- Development of gold nanoparticles (AuNPs) conjugated with a stable variant of human fibroblast growth factor 1 (FGF1), a ligand for all FGFRs.
- Characterization of the FGF1-AuNP conjugates for thermal stability, protease resistance, and biological activity.
- In vitro assessment of selective internalization by FGFR-expressing cells and subsequent cell viability reduction upon near-infrared light irradiation.
Main Results:
- FGF1-AuNP conjugates were specifically internalized by cells overexpressing FGFRs.
- Irradiation with near-infrared light significantly reduced the viability of FGFR-expressing cells (down to 40% of control).
- Cells lacking FGFRs showed no significant reduction in proliferation potential, indicating target specificity.
Conclusions:
- FGF1-coated AuNPs are feasible for targeted cancer therapy.
- This approach offers a potential strategy for infrared-induced thermal ablation of FGFR-overexpressing tumors.
- The use of a stabilized FGF1 variant enhances the therapeutic potential of these nanoconjugates.
