Dataset Information

A polymeric domain that promotes cellular internalization.

ABSTRACT: Polymers have emerged as powerful biological tools; however, their ability to gain access to the intracellular environment is limited. To expand the biological utility of polymer scaffolds, we have synthesized an internalization domain using the ring-opening metathesis polymerization (ROMP). A polymer functionalized with guanidinium groups is effectively internalized by cells and localized in both vesicles and the cytoplasm. Because the synthesis of such materials is modular, we anticipate that compounds of this type can be fashioned that facilitate the delivery of cargo via end-cap derivatization or block copolymer synthesis.

SUBMITTER: Kolonko EM

PROVIDER: S-EPMC3216674 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A polymeric domain that promotes cellular internalization.

Kolonko Erin M EM Kiessling Laura L LL

Journal of the American Chemical Society 20080408 17

Polymers have emerged as powerful biological tools; however, their ability to gain access to the intracellular environment is limited. To expand the biological utility of polymer scaffolds, we have synthesized an internalization domain using the ring-opening metathesis polymerization (ROMP). A polymer functionalized with guanidinium groups is effectively internalized by cells and localized in both vesicles and the cytoplasm. Because the synthesis of such materials is modular, we anticipate that ...[more]

PMID: 18393495

Similar Datasets

Project description:Hepatocytes and acinar cells exhibit high-efficiency, fiber-dependent internalization of adenovirus; however, viral capsids have unpredictable immunological effects and are challenging to develop into targeted drug carriers. To exploit this internalization pathway and minimize the use of viral proteins, we developed a simple gene product that self assembles nanoparticles decorated with the knob domain of adenovirus serotype 5 fiber protein. The most significant advantages of this platform include: (i) compatibility with genetic engineering; (ii) no bioconjugate chemistry is required to link fusion proteins to the nanoparticle surface; and (iii) it can direct the reversible assembly of large nanoparticles, which are monodisperse, multivalent, and biodegradable. These particles are predominantly composed from diblock copolymers of elastin-like polypeptide (ELP). ELPs have unique phase transition behavior, whereby they self-assemble above a transition temperature that is simple to control. The diblock ELP described contains two motifs with distinct transition temperatures, which assemble nanoparticles at physiological temperatures. Analysis by non-denaturing-PAGE demonstrated that the purified knob-ELP formed trimers or dimers, which is a property of the native knob/fiber protein. Dynamic light scattering indicated that the diblock copolymer, with or without knob, is able to self assemble into nanoparticles ~40 nm in diameter. To examine the functionality of knob-ELP, their uptake was assessed in a hepatocyte cell-line that expresses the receptor for adenovirus serotype 5 fiber and knob, the coxsackievirus and adenovirus receptor (CAR). Both plain ELP and knob-ELP were bound to the outside of hepatocytes; however, the knob-ELP fusion protein exhibits more internalization and localization to lysosomes of hepatocytes. These findings suggest that functional fusion proteins may only minimally influence the assembly temperature and diameter of ELP nanoparticles. These results are a proof-of-principal that large fusion proteins (>10 kDa) can be assembled by diblock ELPs without the need for bioconjugate chemistry, which greatly simplifies the design and evaluation of targeted drug carriers.

Dataset Information

A polymeric domain that promotes cellular internalization.

Publications

A polymeric domain that promotes cellular internalization.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets