Architecturally induced multiresponsive vesicles from well-defined polypeptides. Formation of gene vehicles

Hermis Iatrou*, Henrich Frielinghaus, Sirkku Hanski, Nikos Ferderigos, Janne Ruokolainen, Olli Ikkala, Dieter Richter, Jimmy Mays, Nikolaos Hadjichristidis

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

127 Scopus citations

Abstract

A series of novel, partially labeled amphiphilic triblock copolypeptides, PLL-b-PBLG-d7-b-PLL, has been synthesized, where PLL and PBLG-d7 are poly(L-lysine hydrochloride) and poly(γ-benzyl-d7-L-glutamate), respectively. The synthetic approach involved the sequential ring-opening polymerization (ROP) of γ-benzyl-L-glutamate and ∈-Boc-L-lysine N-carboxy anhydrides by a diamino initiator using high-vacuum techniques, followed by the selective deprotection of the Boc groups. Combined characterization results showed that the copolypeptides exhibit high degrees of molecular and compositional homogeneity. The synthesized copolypeptides had similar molecular weights, while the composition of the middle block ranged between 19 and 74% with respect to the monomeric units. Due to the macromolecular architecture of the copolypeptide and the rigid nature of the middle block, the formation of monolayers was favored, and, surprisingly, vesicles were formed in water at neutral pH over the entire compositional range. The vesicular structures were extensively characterized by static and dynamic light scattering, small-angle neutron scattering, atomic force microscopy, cryo-transmission electron microscopy, scanning electron microscopy, UV and Fourier transform infrared spectroscopy, and circular dichroism. In contrast to other vesicular structures derived from conventional polymers, the formed polypeptidic vesicles possess the unique feature of being stimuli-responsive to pH and temperature. When the copolypeptides were mixed with plasmid DNA (pDNA), large vesicular structures were also formed. The molecular characterization of the vectors was performed with most of the methods mentioned above, and indicated that the pDNA is both partially condensed on the PLL phase and partially encapsulated inside the vesicle. Consequently, the synthesized vectors combine the advantages of the polylysine-DNA systems to condense large amounts of genes, as well as those of the liposome-DNA systems to better protect the encapsulated DNA. These vectors are expected to present better gene transfection efficiency to the cell nucleus.

Original languageEnglish (US)
Pages (from-to)2173-2181
Number of pages9
JournalBiomacromolecules
Volume8
Issue number7
DOIs
StatePublished - Jul 1 2007

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

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