Preparation and evaluation of peptide-dendrimer-paclitaxel conjugates for treatment of heterogeneous stage 1 nonsmall cell lung cancer in 293T and L132 cell lines

  • Wei-wei Zhang
  • Yan-chun Wang
  • Xiang-ming Kan
  • Xue-mei Wang
  • Dong-mei Geng
Keywords: Paclitaxel, Lung cancer, Non-small cell lung cancer, Dendrimer, Peptide, PAMAM


Purpose: To develop peptide-dendrimer-paclitaxel conjugates for the treatment of heterogeneous stage 1 non small cell lung cancer (NSCLC) in 293T and L132cell line.

Method: Dendrimer-paclitaxel conjugates (PAMAM-PTX) were prepared by NHS method and the conjugates were used for the synthesis of peptide-dendrimer-paclitaxel conjugates (GE-PAMAM-PTX). The particle sizes of PAMAM-PTX and GE-PAMAM-PTX were measured. Entrapment efficiency of PTX in PAMAM-PTX was measured while GE-PAMAM-PTX. PTX release from PAMAM-PTX and GEPAMAM- PTX was determined using a dialysis bag in pH 7.4 phosphate buffer. The cytotoxicity of PAMAM-PTX, GE-PAMAM-PTX, PAMAM and PTX was evaluated by 3-(4,5-dimethylthiazol-2-Yl)-2,5- diphenyltetrazolium bromide (MTT) assay using 293T cell lines. In vitro cellular uptake assay of PAMAM-PTX and GE-PAMAM-PTX and PTX at concentrations ranging from 0.01 to 0.5μM for 8 h was carried out in NSCLC cell lines 293T and L132.

Results: More than 95 % entrapment efficiency of GE-PAMAM-PTX was observed with loading efficiency of 25 %. GE-PAMAM-PTX conjugates showed sustained release of PTX (~85 %) towards the end of 50 h. GE-PAMAM-PTX conjugates were more cytotoxic than pure PTX and PAMAM-PTX conjugates. The remarkable uptake of GE-PAMAM-PTX appear to be due to receptor-mediated endocytosis in the cell lines. The presence of ligand (GE) on PAMAM-PTX surface enabled the complex to bind to the over-expressed receptors on the cell lines.

Conclusion: GE-PAMAM-PTX can facilitate targeting of paclitaxel to lung cancer cell lines and tumors and facilitate release of the drugs in a sustained manner to improve the therapeutic efficacy of PTX.

Keywords: Paclitaxel, Lung cancer, Non-small cell lung cancer, Dendrimer, Peptide, PAMAM


Journal Identifiers

eISSN: 1596-9827
print ISSN: 1596-5996