Biological-like vesicular structures self-assembled from DNA-block copolymers (original) (raw)
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Macromolecular Rapid Communications, 2009
The ability of amphiphilic block copolymers to self-assemble in selective solvents has been widely studied in academia and utilized for various commercial products. The self-assembled polymer vesicle is at the forefront of this nanotechnological revolution with seemingly endless possible uses, ranging from biomedical to nanometer-scale enzymatic reactors. This review is focused on the inherent advantages in using polymer vesicles over their small molecule lipid counterparts and the potential applications in biology for both drug delivery and synthetic cellular reactors.
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Block copolymer self-assembly is normally conducted via post-polymerization processing at high dilution. In the case of block copolymer vesicles (or "polymersomes"), this approach normally leads to relatively broad size distributions, which is problematic for many potential applications. Herein we report the rational synthesis of lowpolydispersity diblock copolymer vesicles in concentrated solution via polymerization-induced self-assembly using reversible addition−fragmentation chain transfer (RAFT) polymerization of benzyl methacrylate. Our strategy utilizes a binary mixture of a relatively long and a relatively short poly(methacrylic acid) stabilizer block, which become preferentially expressed at the outer and inner poly(benzyl methacrylate) membrane surface, respectively. Dynamic light scattering was utilized to construct phase diagrams to identify suitable conditions for the synthesis of relatively small, low-polydispersity vesicles. Small-angle X-ray scattering (SAXS) was used to verify that this binary mixture approach produced vesicles with significantly narrower size distributions compared to conventional vesicles prepared using a single (short) stabilizer block. Calculations performed using self-consistent mean field theory (SCMFT) account for the preferred self-assembled structures of the block copolymer binary mixtures and are in reasonable agreement with experiment. Finally, both SAXS and SCMFT indicate a significant degree of solvent plasticization for the membrane-forming poly(benzyl methacrylate) chains.
DNA-polymer conjugates have been recognized as versatile functional materials in many different fields ranging from nanotechnology to diagnostics and biomedicine. They combine the favorable properties of nucleic acids and synthetic polymers. Moreover, joining both structures with covalent bonds to form bioorganic hybrids allows for the tuning of specific properties or even the possibility of evolving completely new functions. One important class of this type of material is amphiphilic DNA block copolymers, which, due to microphase separation, can spontaneously adopt nanosized micelle morphologies with a hydrophobic core and a DNA corona. These DNA nano-objects have been explored as vehicles for targeted gene and drug delivery, and also as programmable nanoreactors for organic reactions. Key to the successful realization of these potential applications is that (1) DNA block copolymer conjugates can be fabricated in a fully automated fashion by employing a DNA synthesizer; (2) hydrophobic compounds can be loaded within their interior; and (3) they can be site-specifically functionalized by a convenient nucleic acid hybridization procedure. This chapter aims to broaden the range of biodiagnostic and biomedical applications of these materials by providing a comprehensive outline of the preparation and characterization of multifunctional DNA-polymer nanoparticles. The first reports of DNA-polymer hybrids go back to the late 1980s. In the earliest example, antisense oligonucleotides (ODNs) covalently attached to a poly(l-lysine) backbone were investigated for their ability to inhibit the synthesis of vesicular stomatitis virus proteins; and indeed it was found that these conjugates acted as antiviral agents (1). With this as a starting point, various applications
Self-assembly of DNA-polymer complexes using template polymerization
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The self-assembly of supramolecular complexes of nucleic acids and polymers is of relevance to several biological processes including viral and chromatin formation as well as gene therapy vector design. We now show that template polymerization facilitates condensation of DNA into particles that are <150 nm in diameter. Inclusion of a poly(ethylene glycol)-containing monomer prevents aggregation of these particles. The DNA within the particles remains biologically active and can express foreign genes in cells. The formation or breakage of covalent bonds has until now not been employed to compact DNA into artificial particles.
Molecular Recognition Induced Self-Assembly of Diblock Copolymers: Microspheres to Vesicles
Macromolecular Bioscience, 2010
Random diblock copolymer scaffolds grafted with diamidopyridine (DAP) hydrogen bonding recognition units self-assembled to furnish microspheres when mixed with monoblock copolymers decorated with complementary recognition elements. Through choice of block length, microspheres of various sizes could be produced. The relative length of the two blocks plays a crucial role in determining the formation of aggregates. PEG-b-P(S-co-S DAP ) diblock copolymer was used to fabricate recognition induced pegylated microspheres, by non-covalent crosslinking with monoblock copolymer functionalized with complementary thymine (Thy) units. These self-assembled microspheres can be efficiently crosslinked via photochemical [2p s þ 2p s ] cycloaddition with the resultant morphology change into vesicular structures.
Functionalization of Block Copolymer Vesicle Surfaces
Polymers, 2011
In dilute aqueous solutions certain amphiphilic block copolymers self-assemble into vesicles that enclose a small pool of water with a membrane. Such polymersomes have promising applications ranging from targeted drug-delivery devices, to biosensors, and nanoreactors. Interactions between block copolymer membranes and their surroundings are important factors that determine their potential biomedical applications. Such interactions are influenced predominantly by the membrane surface. We review methods to functionalize block copolymer vesicle surfaces by chemical means with ligands such as antibodies, adhesion moieties, enzymes, carbohydrates and fluorophores. Furthermore, surface-functionalization can be achieved by self-assembly of polymers that carry ligands at their chain ends or in their hydrophilic blocks. While this review focuses on the strategies to functionalize vesicle surfaces, the applications realized by, and envisioned for, such functional polymersomes are also highlighted.