title: Functionalized gold nanoparticles improve afatinib delivery into cancer cells.
abstract: OBJECTIVE
  A drug delivery system based on colloidal pegylated gold nanoparticles (PEGAuNPs) conjugated with the tyrosine kinase inhibitor afatinib was designed and tested for enhancing the drug activity against pancreatic and NSCLC cells.
  
  
  METHODS
  PEGAuNPs were synthesized and characterized physicochemically. Confocal imaging was performed to evaluate the nanoparticle (NP) internalization in cancer cells. For cell-cycle distribution analysis, conjugated NPs and afatinib alone were incubated with cells and alterations on the cell-cycle profile subsequently analyzed by total DNA staining. Cancer cell survival and growth inhibition following incubation with afatinib and PEGAuNPs-afatinib (concentrations between 0.007 and 0.500 µM afatinib) were evaluated.
  
  
  RESULTS
  A higher cellular uptake of PEGAuNPs was observed by cancer cells. Our data suggest an efficient conjugation of PEGAuNPs with the drug, enhancing the afatinib activity in comparison with afatinib alone. In fact, IC50 and GI50 results obtained show that the PEGAuNPs-afatinib conjugate is ca. 5 and 20 times more potent than afatinib alone in S2-013 and A549 cell lines, respectively.
  
  
  CONCLUSIONS
  Conjugating PEGAuNPs with afatinib is a promising antitumor delivery system for cancer therapy as it improves drug efficacy, allowing a reduction in drug dose used and minimizing possible toxicity-related side effects.
authors.affiliation: a 1 University of Porto, LEPABE, Faculty of Engineering, Department of Chemical Engineering , Rua Roberto Frias, PT-4200-465 Porto, Portugal +351 225 081 679 ; +351 225 081 449 ; silvia.coelho@fe.up.pt.
authors.forename: Sílvia Castro
authors.initials: SC
authors.lastname: Coelho
authors.affiliation: b 2 Universidade do Porto, Instituto de Investigação e Inovação em Saúde , Porto, Portugal.|c 3 IPATIMUP, Expression Regulation in Cancer Group , Porto, Portugal.
authors.forename: Gabriela M
authors.initials: GM
authors.lastname: Almeida
authors.affiliation: a 1 University of Porto, LEPABE, Faculty of Engineering, Department of Chemical Engineering , Rua Roberto Frias, PT-4200-465 Porto, Portugal +351 225 081 679 ; +351 225 081 449 ; silvia.coelho@fe.up.pt.
authors.forename: Maria Carmo
authors.initials: MC
authors.lastname: Pereira
authors.affiliation: b 2 Universidade do Porto, Instituto de Investigação e Inovação em Saúde , Porto, Portugal.|d 4 IPATIMUP, Public Awareness of Cancer Unit , Porto, Portugal.|e 5 University of Porto, Faculty of Medicine , Porto, Portugal.|f 6 University of Nebraska Medical Center, Eppley Institute, Department of Biochemistry and Molecular Biology , Omaha, NE, USA.
authors.forename: Filipe
authors.initials: F
authors.lastname: Santos-Silva
authors.affiliation: a 1 University of Porto, LEPABE, Faculty of Engineering, Department of Chemical Engineering , Rua Roberto Frias, PT-4200-465 Porto, Portugal +351 225 081 679 ; +351 225 081 449 ; silvia.coelho@fe.up.pt.
authors.forename: Manuel A N
authors.initials: MA
authors.lastname: Coelho
mesh_terms: D000077716:Afatinib; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006046:Gold; D006801:Humans; D020128:Inhibitory Concentration 50; D053758:Nanoparticles / Q000737:chemistry*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000737:chemistry; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011799:Quinazolines / Q000008:administration & dosage*
chemical_list: D011799:Quinazolines; D011092:Polyethylene Glycols; D000077716:Afatinib; D006046:Gold; D011505:Protein-Tyrosine Kinases
keywords: NSCLC; afatinib; gold nanoparticles; irreversible covalent inhibitor of the receptor tyrosine; pancreatic cancer cells