Multimeric peptide-based PEG nanocarriers with programmable elimination properties

Simi Gunaseelan, Shahriar Pooyan, Peiming Chen, Mahta Samizadeh, Matthew S. Palombo, Stanley Stein, Xiaoping Zhang, Patrick J. Sinko

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

In the current study, the design, synthetic feasibility and biochemical characterization of biodegradable peptidic PEG-based nanocarriers are described. The components were selected to influence the body elimination pathway upon nanocarrier biodegradation. Two prototypical nanocarriers were prepared using non-PEGylated and PEGylated peptidic cores [CH3CO-(Lys-βAla-βAla)X-Cys-CONH2 (X = 2, 4)]. A homodimeric nanocarrier with 4 copies of fluorescein-PEG5kDa was synthesized by linking two PEGylated peptidic cores (X = 2) using a disulfide bond. A dual labeled heterodimeric nanocarrier with 2 copies of fluorescein-PEG5kDa and 4 copies of Texas Red was also synthesized. Optimum conditions for linking imaging agents, PEG, or a peptidic core to a peptidic core were determined. Significantly higher yields (69% versus 30%) of the PEGylated peptidic core were obtained by using 2 copies of β-alanine as a spacer along with increasing DMSO concentrations, which resulted in reduced steric hindrance. Stoichiometric addition of the components was also demonstrated and found to be important for reducing polydispersity. Nanocarrier biodegradation was evaluated in simulated intracellular and extracellular/blood environments using 3 mm and 10 μm glutathione in buffer, respectively. The nanocarrier was 9-fold more stable in the extracellular environment. The results suggest selective intracellular degradation of the nanocarrier into components with known body elimination pathways.

Original languageEnglish (US)
Pages (from-to)5649-5659
Number of pages11
JournalBiomaterials
Volume30
Issue number29
DOIs
StatePublished - Oct 2009

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Keywords

  • Disulfide
  • GSH-dependent biodegradation
  • Intracellular elimination
  • Nanocarrier
  • PEG
  • Peptide

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