EGF Functionalized Polymer-Coated Gold Nanoparticles Promote EGF Photostability and EGFR Internalization for Photothermal Therapy

PLoS One. 2016 Oct 27;11(10):e0165419. doi: 10.1371/journal.pone.0165419. eCollection 2016.

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.

MeSH terms

  • A549 Cells
  • Cell Survival / drug effects
  • Drug Carriers / chemistry
  • Drug Carriers / toxicity
  • Epidermal Growth Factor / chemistry*
  • Epidermal Growth Factor / pharmacology*
  • ErbB Receptors / metabolism*
  • Gold / chemistry*
  • Gold / toxicity
  • Humans
  • Hyaluronic Acid / chemistry
  • Light
  • Metal Nanoparticles / chemistry*
  • Oleic Acid / chemistry
  • Phototherapy*
  • Polymers / chemistry*
  • Protein Stability / radiation effects
  • Protein Transport / drug effects
  • Protein Transport / radiation effects
  • Temperature

Substances

  • Drug Carriers
  • Polymers
  • Oleic Acid
  • Epidermal Growth Factor
  • Gold
  • Hyaluronic Acid
  • ErbB Receptors

Grants and funding

Support was provided by: Fundação para a Ciência e Tecnologia (FCT) for the financial support under the project reference PTDC/BBB-BMC/0611/2012 [https://www.fct.pt/apoios/projectos)]. The work at CBMA was supported by the strategic programme UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569) funded by national funds through the FCT I.P. and by the ERDF through the COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI) [https://www.fct.pt/apoios/projectos]; European Commission through the project H2020-644242 –SAPHELY (https://saphely.eu/project.php) and the project H2020-634013-2-PHOCNOSIS [http://cordis.europa.eu/project/rcn/193268_en.html].