FGF1-gold nanoparticle conjugates targeting FGFR efficiently decrease cell viability upon NIR irradiation

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.

Keywords:

• FGF1-conjugates
• gold nanoparticles
• FGFR-targeted cancer therapy
• photothermal therapy

Acknowledgements

This work was supported by the Wroclaw Research Center EIT+ under the project Biotechnologies and advanced medical technologies – BioMed (POIG 01.01.02-02-003/08-00) financed from the European Regional Development Fund (Operational Program Innovative Economy, 1.1.2).

We thank Dr Michal Majkowski from the Laboratory of Cytobiochemistry, University of Wroclaw; Dr Jorgen Wesche from the Department of Biochemistry, Institute for Cancer Research; the Norwegian Radium Hospital for help with confocal microscopy experiments; and the skillful technical assistance of Anne Engen and Anne-Mari G Pedersen from the Department of Biochemistry, Institute for Cancer Research. The Norwegian Radium Hospital is gratefully acknowledged.

Disclosure

The authors report no conflicts of interest in this work.