Oligo(ethylene glycol)-based thermosensitive dendrimers and their tumor accumulation and penetration

J Am Chem Soc. 2014 Feb 26;136(8):3145-55. doi: 10.1021/ja411457r. Epub 2014 Feb 18.


Dendrimers have several featured advantages over other nanomaterials as drug carriers, such as well-defined structure, specific low-nanometer size, and abundant peripheral derivable groups, etc. However, these advantages have not been fully exploited yet to optimize their biological performance, especially tumor penetration, which is a shortcoming of current nanomaterials. Here we show the syntheses of a new class of oligo(ethylene glycol) (OEG)-based thermosensitive dendrimers up to the fourth generation. Each dendrimer shows monodisperse structure. OEG/poly(ethylene glycol) (PEG) moieties with different precise lengths were introduced to the periphery of the fourth-generation dendrimer followed by an antitumor agent, gemcitabine (GEM). The biodistributions of the GEM-conjugated dendrimers were investigated by micro positron emission tomography and multispectral optoacoustic tomography imaging techniques and compared with that of GEM-conjugated poly(amidoamine) (PAMAM). The GEM-conjugated dendrimer with the longest peripheral PEG segments exhibited the most desirable tumor accumulation and penetration and thus had significantly higher antitumor activity than the GEM-conjugated PAMAM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Dendrimers / chemical synthesis*
  • Dendrimers / chemistry
  • Dendrimers / pharmacology
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacology
  • Drug Carriers / chemical synthesis*
  • Drug Carriers / chemistry
  • Drug Carriers / pharmacology
  • Female
  • Flow Cytometry
  • Mice
  • Microscopy, Electron, Transmission
  • Polyethylene Glycols / chemical synthesis*
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / pharmacology
  • Positron-Emission Tomography


  • Antineoplastic Agents
  • Dendrimers
  • Drug Carriers
  • Deoxycytidine
  • Polyethylene Glycols
  • gemcitabine