Functionalized gold nanoparticles improve afatinib delivery into cancer cells

Abstract

Objectives: 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.

Keywords:

• afatinib
• gold nanoparticles
• irreversible covalent inhibitor of the receptor tyrosine
• NSCLC
• pancreatic cancer cells

Acknowledgments

We gratefully acknowledge Prof. MA Hollingsworth (University of Nebraska Medical Center – Omaha, USA) for kindly providing the human pancreatic cell lines (S2-013). We gratefully acknowledge Dr GDD Jones (University of Leicester, UK) for kindly providing the human NSCLC cell line A549. We would like to thank Dr P Sampaio for the collaboration with confocal work analysis.

Declaration of interest

This work was supported by financial support by TRANSCAN-FCT (research project TRANSCAN/0001/2012) and Portuguese Cancer League. IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT, the Portuguese Foundation for Science and Technology. GM Almeida was supported by the Investigator FCT Program 2013 (IF/00615/2013), POPH - QREN Type 4.2, European Social Fund and Portuguese Ministry of Science and Technology (MCTES). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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