Orthogonal and modular approaches for the construction of nanostructured hybrid polymers

X. Jia
University of Delaware, US

Keywords: nanopolymers


Rapid and bioorthogonal reactions, when combined with modular building blocks, enable the construction of polymeric materials with complex molecular architecture, tunable mechanical properties and unique nanoscale organizations. For example, elastin mimetic hybrid polymers (EMHPs) composed of poly(ethylene glycol) (PEG) alternating with an alanine-rich, lysine-containing peptide [(AKA3KA)2, AK2], with or without the cell-binding domains, were synthesized by condensation polymerization employing copper (I) catalyzed alyne-azide cycloaddition (CuAAC) reaction. Covalent crosslinking of [PEG-AK2]n through the lysine amines afforded cell-adhesive, elastomeric hydrogels. Separately, EMHPs consisting of poly(acrylic acid) (PAA) alternating with a elastin-based peptide [(VPGVG)2 (VG2)] have also been successfully synthesized under CuAAC conditions. [PAA-VG2]n self-assembled into discrete nanoparticles through the concerted interactions between the constituent building blocks. Recently, tetrazine ligation, an ultrafast cycloaddition of s-tetrazine (Tz) with trans-cyclooctene (TCO) derivatives, was employed for the synthesis of multiblock copolymers using homo-difunctional Tz and TCO derivatives as the building blocks. Judicial selection of the monomeric building blocks allowed for the polymerization to be carried out at the immiscible solvent interface. As the polymerization proceeded, high molecular weight polymer fibers were pulled out of the interface. Compared to the corresponding solution phase polymerization, the interfacial process gave rise to polymers with a higher molecular weight and a narrower molecular weight distribution. Inspection of the micron-sized fibers by FIB-SEM revealed the presence of nanosized pores in the fiber interior. Introduction of RGD-based peptidic building block in the monomer mixture resulted in a quantitative incorporation of the peptide in the resultant copolymers. The modular approaches allow facile substitution of the polymer and peptide segments to fine-tune the materials properties for applications in tissue engineering and drug delivery.