Tyrosine kinase inhibitor conjugated quantum dots for non-small cell lung cancer (NSCLC) treatment

Eur J Pharm Sci. 2019 May 15:133:145-159. doi: 10.1016/j.ejps.2019.03.026. Epub 2019 Apr 1.


Non-small cell lung cancer is a major sub-type of lung cancer that is associated with a poor diagnosis resulting in poor therapy for the disorder. In order to achieve a better prognosis, innovative multi-functional systems need to be developed which will aide in diagnosis as well as therapy for the disorder. One such multi-functional delivery system fabricated is Quantum Dots (QDs). QDs are photo-luminescent inorganic nanoparticles utilized for tumor detection, preclinically. Erlotinib hydrochloride, a tyrosine kinase inhibitor, is a first-generation drug developed to treat NSCLC. Its active metabolite, Desmethyl Erlotinib (OSI-420), exhibits similar anticancer activity as erlotinib. OSI-420 was conjugated to QDs to fabricate a delivery system and was then characterized by FT-IR, H NMR, UV-VIS, particle size, zeta potential, fluorescence spectroscopy and TEM. Drug loading was estimated using UV-VIS spectroscopy (52.2 ± 7.5%). A concentration-dependent release of OSI-420 was achieved using esterase enzymes, which was further confirmed using LC-MS. A cellular uptake study revealed the internalization potential of QDs and QD-OSI 420. A cellular recovery study was performed to confirm the internalization potential. Cell viability studies revealed that QD-OSI 420 conjugates had significantly better efficacy than pure drugs in all tested cell lines. QD conjugated OSI-420 demonstrated an IC60 of 2.5 μM in erlotinib-resistant A549 cell lines, where erlotinib or OSI-420 alone could not exhibit 60% inhibition when evaluated up to 20 μM. Similar cytotoxic enhancement of erlotinib was seen with QD-OSI 420 in other NSCLC cell lines as well. These results were strengthened by 3D-SCC model of A549 which revealed that QD-OSI 420 was significantly better in reducing in-vitro 3D tumor volume, as compared to pure drugs. This study, being one of its kind, explores the feasibility of conjugating OSI-420 with QDs as an alternative to traditional anti-cancer therapy, by improving intracellular drug delivery.

Keywords: 3D-spheroid cell culture; Drug delivery; Erlotinib; OSI-420; Quantum dots.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Cell Line
  • Cell Survival / drug effects
  • Drug Liberation
  • Esterases / chemistry
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lysosomes / metabolism
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / chemistry
  • Quantum Dots / administration & dosage*
  • Quantum Dots / chemistry
  • Quinazolines / administration & dosage*
  • Quinazolines / chemistry


  • OSI-420
  • Protein Kinase Inhibitors
  • Quinazolines
  • Esterases