Synthesis and in vivo antitumor efficacy of PEGylated poly(L-lysine) dendrimer-camptothecin conjugates

Megan E. Fox, Steve Guillaudeu, Jean M.J. Fréchet, Katherine Jerger, Nichole Macaraeg, Francis C. Szoka

Research output: Contribution to journalArticlepeer-review

147 Scopus citations


Polymer conjugates of camptothecin (CPT) have been pursued as a solution to the difficulties present in treating cancers with CPT and its derivatives. Covalent attachment of CPT to a polymer can improve solubility, increase blood circulation time, enhance tumor uptake, and significantly improve efficacy of the drug. In this report, we describe a novel polymer conjugate of CPT using a core-functionalized, symmetrically PEGylated poly(L-lysine) (PLL) dendrimer. The PEGylated dendrimer consisted of a lysine dendrimer functionalized with aspartic acid, which was used as an attachment site for poly(ethylene glycol) (PEG) and CPT. The final conjugate had a molecular weight of 40 kDa and was loaded with 4-6 wt % CPT. Polymer-bound CPT was shown to have a long blood circulation half-life of 30.9 ± 8.8 h and a tumor uptake of 4.2 ± 2.3% of the injected dose/g of tissue, compared to free CPT in which less than 1% was retained in the blood after 30 min and had a tumor accumulation of 0.29 ± 0.04% of the injected dose/g of tissue. The PEGylated PLL-CPT showed superior efficacy in murine (C26) and human colon carcinoma (HT-29) tumor models when compared with no treatment or treatment with irinotecan. In the C26 tumor model, treatment resulted in significantly prolonged survival (P < 0.05) for all mice treated with a single injection of PEGylated PLL-CPT. In the HT-29 tumor model, all mice treated with multiple injections of a low dose survived to the end of the study, with three mice of eight surviving tumor-free.

Original languageEnglish (US)
Pages (from-to)1562-1572
Number of pages11
JournalMolecular Pharmaceutics
Issue number5
StatePublished - Oct 5 2009
Externally publishedYes


  • Camptothecin
  • Colon carcinoma
  • Dendrimer
  • Drug delivery
  • PEG
  • Poly(L-lysine)

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery


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