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PAMAM dendrimer-based multifunctional conjugate for cancer therapy: synthesis, characterization, and functionality.

Abstract
Poly(amidoamine) (PAMAM) dendrimer-based multifunctional cancer therapeutic conjugates have been designed and synthesized. The primary amino groups on the surface of the generation 5 (G5) PAMAM dendrimer were neutralized through partial acetylation, providing enhanced solubility of the dendrimer (in conjugation of FITC (fluorescein isothiocyanate)) and preventing nonspecific targeting interactions (in vitro and in vivo) during delivery. The functional molecules fluorescein isothiocyanate (FITC, an imaging agent), folic acid (FA, targets overexpressed folate receptors on specific cancer cells), and paclitaxel (taxol, a chemotherapeutic drug) were conjugated to the remaining nonacetylated primary amino groups. The appropriate control dendrimer conjugates have been synthesized as well. Characterization of the G5 PAMAM dendrimer and its nanosize conjugates, including the molecular weight and number of primary amine groups, has been determined by multiple analytical methods such as gel permeation chromatography (GPC), nuclear magnetic resonance spectroscopy (NMR), potentiometric titration, high-performance liquid chromatography (HPLC), and UV spectroscopy. These multifunctional dendrimer conjugates have been tested in vitro for targeted delivery of chemotherapeutic and imaging agents to specific cancer cells. We present here the synthesis, characterization, and functionality of these dendrimer conjugates.
AuthorsIstván J Majoros, Andrzej Myc, Thommey Thomas, Chandan B Mehta, James R Baker Jr
JournalBiomacromolecules (Biomacromolecules) Vol. 7 Issue 2 Pg. 572-9 (Feb 2006) ISSN: 1525-7797 [Print] United States
PMID16471932 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Dendrimers
  • Drug Carriers
  • PAMAM Starburst
  • Polyamines
  • Folic Acid
  • Fluorescein-5-isothiocyanate
  • Paclitaxel
Topics
  • Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
  • Cell Proliferation (drug effects)
  • Dendrimers (chemical synthesis, chemistry, pharmacology)
  • Drug Carriers (chemical synthesis, chemistry, pharmacology)
  • Drug Design
  • Drug Screening Assays, Antitumor
  • Flow Cytometry
  • Fluorescein-5-isothiocyanate (chemistry)
  • Folic Acid (chemistry)
  • Humans
  • KB Cells
  • Molecular Conformation
  • Molecular Weight
  • Paclitaxel (chemistry)
  • Polyamines (chemical synthesis, chemistry, pharmacology)

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