Preclinical antitumor efficacy evaluation of dendrimer-based methotrexate conjugates

Anticancer Drugs. 2008 Feb;19(2):143-9. doi: 10.1097/CAD.0b013e3282f28842.


Our previous studies have demonstrated the in-vitro and in-vivo targeting of a generation-5 (G5) dendrimer-based multifunctional conjugate, which used folic acid (FA) as the targeting agent and methotrexate (MTX) as the chemotherapeutic drug. For the synthesized G5-FA-MTX nanodevice conjugate to be clinically applicable as a cancer therapeutic drug, it is important that the compound elicits cytotoxicity specifically and consistently. The aim of this work was to evaluate four independently synthesized batches of G5-FA-MTX conjugates for their cytotoxic potential and specificity. For determination of specificity, we have used a unique 'coculture' assay in which FA receptor-positive and FA receptor-negative cells were cultured together and have examined the preferential killing of the former. The results of our study show the batch-to-batch consistency and specificity of the G5-FA-MTX nanodevice in the preferential killing of FA receptor-positive cells. The coculture assay shows the consistency of the four different G5-FA-MTX conjugate lots in the specific killing of targeted cells. Further in-vivo studies are, however, necessary to prove the clinical potential of this targeted therapeutic nanodevice.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antimetabolites, Antineoplastic / chemistry
  • Antimetabolites, Antineoplastic / pharmacology*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Coculture Techniques
  • Dendrimers
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor / methods
  • Flow Cytometry
  • Folate Receptors, GPI-Anchored
  • Folic Acid / chemistry
  • Folic Acid / metabolism
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • KB Cells
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Methotrexate / chemistry
  • Methotrexate / pharmacology*
  • Microscopy, Fluorescence
  • Plasmids / chemistry
  • Plasmids / genetics
  • Polyamines / chemistry*
  • Polyamines / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Transfection
  • Tumor Stem Cell Assay / methods


  • Antimetabolites, Antineoplastic
  • Carrier Proteins
  • Dendrimers
  • Folate Receptors, GPI-Anchored
  • Luminescent Proteins
  • PAMAM Starburst
  • Polyamines
  • Receptors, Cell Surface
  • red fluorescent protein
  • Green Fluorescent Proteins
  • Folic Acid
  • Methotrexate