title: EGF Functionalized Polymer-Coated Gold Nanoparticles Promote EGF Photostability and EGFR Internalization for Photothermal Therapy.
abstract: The application of functionalized nanocarriers on photothermal therapy for cancer ablation has wide interest. The success of this application depends on the therapeutic efficiency and biocompatibility of the system, but also on the stability and biorecognition of the conjugated protein. This study aims at investigating the hypothesis that EGF functionalized polymer-coated gold nanoparticles promote EGF photostability and EGFR internalization, making these conjugated particles suitable for photothermal therapy. The conjugated gold nanoparticles (100-200 nm) showed a plasmon absorption band located within the near-infrared range (650-900 nm), optimal for photothermal therapy applications. The effects of temperature, of polymer-coated gold nanoparticles and of UVB light (295nm) on the fluorescence properties of EGF have been investigated with steady-state and time-resolved fluorescence spectroscopy. The fluorescence properties of EGF, including the formation of Trp and Tyr photoproducts, is modulated by temperature and by the intensity of the excitation light. The presence of polymeric-coated gold nanoparticles reduced or even avoided the formation of Trp and Tyr photoproducts when EGF is exposed to UVB light, protecting this way the structure and function of EGF. Cytotoxicity studies of conjugated nanoparticles carried out in normal-like human keratinocytes showed small, concentration dependent decreases in cell viability (0-25%). Moreover, conjugated nanoparticles could activate and induce the internalization of overexpressed Epidermal Growth Factor Receptor in human lung carcinoma cells. In conclusion, the gold nanoparticles conjugated with Epidermal Growth Factor and coated with biopolymers developed in this work, show a potential application for near infrared photothermal therapy, which may efficiently destroy solid tumours, reducing the damage of the healthy tissue.
authors: Research Center for Biosciences & Health Technologies, Universidade Lusófona, Lisboa, Portugal.|Department of Biomedical Sciences, Faculty of Pharmacy, University of Alcalá, Alcalá de Henares, Spain.
authors: Catarina Oliveira
authors: CO
authors: Silva
authors: Medical Photonics Lab, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark.
authors: Steffen B
authors: SB
authors: Petersen
authors: Research Center for Biosciences & Health Technologies, Universidade Lusófona, Lisboa, Portugal.|IBEB, Biophysics and Biomedical Engineering, Faculty of Sciences, University of Lisbon, Lisbon, Portugal.
authors: Catarina Pinto
authors: CP
authors: Reis
authors: Research Center for Biosciences & Health Technologies, Universidade Lusófona, Lisboa, Portugal.|iMed.ULisboa, Instituto de Investigação do Medicamento, Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal.
authors: Patrícia
authors: P
authors: Rijo
authors: Department of Biomedical Sciences, Faculty of Pharmacy, University of Alcalá, Alcalá de Henares, Spain.
authors: Jesús
authors: J
authors: Molpeceres
authors: Research Center for Biosciences & Health Technologies, Universidade Lusófona, Lisboa, Portugal.|iMed.ULisboa, Instituto de Investigação do Medicamento, Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal.
authors: Ana Sofia
authors: AS
authors: Fernandes
authors: Medical Photonics Lab, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark.|CBMA (Centre of Molecular and Environmental Biology), University of Minho, Campus de Gualtar, Braga, Portugal.|CFUM (Centre of Physics of University of Minho), Department of Physics, University of Minho, Campus de Gualtar, Braga, Portugal.
authors: Odete
authors: O
authors: Gonçalves
authors: CBMA (Centre of Molecular and Environmental Biology), University of Minho, Campus de Gualtar, Braga, Portugal.
authors: Andreia C
authors: AC
authors: Gomes
authors: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.
authors: Isabel
authors: I
authors: Correia
authors: Department of Ophthalmology, Aalborg University Hospital, Aalborg, Denmark.
authors: Henrik
authors: H
authors: Vorum
authors: Department of Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark.
authors: Maria Teresa
authors: MT
authors: Neves-Petersen
mesh_terms: D000072283:A549 Cells; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry / Q000633:toxicity; D004815:Epidermal Growth Factor / Q000737:chemistry* / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism*; D006046:Gold / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry; D008027:Light; D053768:Metal Nanoparticles / Q000737:chemistry*; D019301:Oleic Acid / Q000737:chemistry; D010789:Phototherapy; D011108:Polymers / Q000737:chemistry*; D055550:Protein Stability / Q000528:radiation effects; D021381:Protein Transport / Q000187:drug effects / Q000528:radiation effects; D013696:Temperature
chemical_list: D004337:Drug Carriers; D011108:Polymers; D019301:Oleic Acid; D004815:Epidermal Growth Factor; D006046:Gold; D006820:Hyaluronic Acid; D066246:ErbB Receptors