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 non-small cell lung cancer cells. Methods: PEGAuNPs were synthesized and characterized physicochemically. Confocal imaging was performed to evaluate the nanoparticle internalization in cancer cells. For cell cycle distribution analysis, conjugated nanoparticles 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 antitumour delivery system for cancer therapy as it improves drug efficacy, allowing to decrease the dose of drug used and minimizing possible toxicity related side effects.

Enhancing the efficiency of bortezomib conjugated to pegylated gold nanoparticles: an in vitro study on human pancreatic cancer cells and adenocarcinoma human lung alveolar basal epithelial cells

“…This fact corroborated with the higher increase in the in vitro cytotoxicity verified to cells incubated with conjugated BTZ than with free BTZ ( Figure 5). Previous studies have demonstrated that PEGAuNPs did not affect the cell survival for the concentration range of 0.1 to 1.0 nM [15,23]. The cell survival of S2-013 and TERT-HPNE cells after exposure was found to be in the range of 42-5 % and 90-38 %, respectively, for a range of BTZ concentration of 0.01-2.93 µM ( Figure 5).…”

“…They present high biocompatibility, stability and easy conjugation, non-toxicity and good uptake on human cells [15,16]. Recently, gold-based nanoparticles have been used to develop new agents as cancer imaging probes [17,18], as agents to enhance radiation therapy [19][20][21][22] and as drug delivery systems for cancer treatment [23][24][25]. Several studies reported that AuNPs in combination with chemotherapy and radiotherapy improve therapy efficacy in different cancer types, including pancreatic and human lung cancers [15,[26][27][28].…”

“…Gold nanoparticles are reported to increase the drug toxicity compared to free drug [4,15,23,29,30]. This fact occurs by passive targeting through EPR effect [31].…”

Next‐Generation Cancer‐Specific Hybrid Theranostic Nanomaterials: MAGE‐A3 NIR Persistent Luminescence Nanoparticles Conjugated to Afatinib for In Situ Suppression of Lung Adenocarcinoma Growth and Metastasis

“…The challenges of developing theranostics for lung cancer metastasis treatment include determining a specific receptor and ensuring the biological safety of the multi‐functional nanocarrier. [ 21–23 ]…”

A novel pH-sensitive liposome to trigger delivery of afatinib to cancer cells: Impact on lung cancer therapy

“…By targeting ErbB family receptors, AFT blocks a wide spectrum of cancer-associated ErbB-driven pathways, and thus has broader antitumor activity against receptors with acquired mutations that are resistant to the first generation of TKIs [13]. AFT exposed at low concentration in the tumor cells, which reduced their clinical uses [14]. Therefore, the targeted delivery of AFT has become a focus of scientific research.…”