Targeting hepatic cancer cells with pegylated dendrimers displaying N-Acetylgalactosamine and SP94 peptide ligands

Scott H. Medina, Gopinath Tiruchinapally, Maxim V. Chevliakov, Yasemin Yuksel Durmaz, Rachell N. Stender, William D. Ensminger, Donna S. Shewach, Mohamed E.H. Elsayed

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Poly(amidoamine) (PAMAM) dendrimers are branched water-soluble polymers defined by consecutive generation numbers (Gn) indicating a parallel increase in size, molecular weight, and number of surface groups available for conjugation of bioactive agents. In this article, we compare the biodistribution of N-acetylgalactosamine (NAcGal)-targeted [14C]1-G5-(NH2)5-(Ac)108-(NAcGal)14 particles to non-targeted [14C]1-G5-(NH2)127 and PEGylated [14C]1-G5-(NH2)44-(Ac)73-(PEG)10 particles in a mouse hepatic cancer model. Results show that both NAcGal-targeted and non-targeted particles are rapidly cleared from the systemic circulation with high distribution to the liver. However, NAcGal-targeted particles exhibited 2.5-fold higher accumulation in tumor tissue compared to non-targeted ones. In comparison, PEGylated particles showed a 16-fold increase in plasma residence time and a 5-fold reduction in liver accumulation. These results motivated us to engineer new PEGylated G5 particles with PEG chains anchored to the G5 surface via acid-labile cis-aconityl linkages where the free PEG tips are functionalized with NAcGal or SP94 peptide to investigate their potential as targeting ligands for hepatic cancer cells as a function of sugar conformation (α versus β), ligand concentration (100-4000 nM), and incubation time (2 and 24 hours) compared to fluorescently (Fl)-labeled and non-targeted G5-(Fl)6-(NH2)122 and G5-(Fl)6-(Ac)107-(cPEG)15 particles. Results show G5-(Fl)6-(Ac)107-(cPEG[NAcGalβ])14 particles achieve faster uptake and higher intracellular concentrations in HepG2 cancer cells compared to other G5 particles while escaping the non-specific adsorption of serum protein and phagocytosis by Kupffer cells, which make these particles the ideal carrier for selective drug delivery into hepatic cancer cells.

Original languageEnglish (US)
Pages (from-to)1337-1350
Number of pages14
JournalAdvanced Healthcare Materials
Issue number10
StatePublished - Oct 2013

All Science Journal Classification (ASJC) codes

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science


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