title: Multifunctional dendrimer/combretastatin A4 inclusion complexes enable in vitro targeted cancer therapy.
abstract: BACKGROUND
  We report here a unique approach to using multifunctional dendrimer/combretastatin A4 (CA4) inclusion complexes for targeted cancer therapeutics.
  
  
  METHODS
  Amine-terminated generation 5 polyamidoamine dendrimers were first partially acetylated to neutralize a significant portion of the terminal amines, and then the remaining dendrimer terminal amines were sequentially modified with fluorescein isothiocyanate as an imaging agent and folic acid as a targeting ligand. The multifunctional dendrimers formed (G5.NHAc-FI-FA) were utilized to encapsulate the anticancer drug, CA4, for targeted delivery into cancer cells overexpressing folic acid receptors.
  
  
  RESULTS
  The inclusion complexes of G5.NHAc-FI-FA/CA4 formed were stable and are able to significantly improve the water solubility of CA4 from 11.8 to 240 μg/mL. In vitro release studies showed that the multifunctional dendrimers complexed with CA4 could be released in a sustained manner. Both 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay and morphological cell observation showed that the inhibitory effect of the G5.NHAc-FI-FA/CA4 complexes was similar to that of free CA4 at the same selected drug concentration. More importantly, the complexes were able to target selectively and display specific therapeutic efficacy to cancer cells overexpressing high-affinity folic acid receptors.
  
  
  CONCLUSIONS
  Multifunctional dendrimers may serve as a valuable carrier to form stable inclusion complexes with various hydrophobic anticancer drugs with improved water solubility, for targeting chemotherapy to different types of cancer.
authors.affiliation: State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai, People's Republic of China.
authors.forename: Mengen
authors.initials: M
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.forename: Xueyan
authors.initials: X
authors.lastname: Cao
authors.forename: Mingwu
authors.initials: M
authors.lastname: Shen
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Shi
mesh_terms: D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry* / Q000494:pharmacology; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D005492:Folic Acid / Q000737:chemistry; D006801:Humans; D007624:KB Cells; D008858:Microscopy, Phase-Contrast; D012995:Solubility; D013267:Stilbenes / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D050091:Dendrimers; C104700:PAMAM Starburst; D013267:Stilbenes; D005492:Folic Acid; D016650:Fluorescein-5-isothiocyanate; C058728:fosbretabulin
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