title: 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.
authors.affiliation: Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Szlachcic
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Pala
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Zakrzewska
authors.forename: Piotr
authors.initials: P
authors.lastname: Jakimowicz
authors.forename: Antoni
authors.initials: A
authors.lastname: Wiedlocha
authors.forename: Jacek
authors.initials: J
authors.lastname: Otlewski
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D016220:Fibroblast Growth Factor 1 / Q000493:pharmacokinetics*; D006046:Gold / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D007259:Infrared Rays / Q000627:therapeutic use; D053768:Metal Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000628:therapy*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D016220:Fibroblast Growth Factor 1; D006046:Gold; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1