The goal of the project is to design new macromolecular structures, whose assembly into hybrid hydrogels will be modulated by association of coiled-coil peptide domains. N-(2-hydroxypropyl)rnethacrylamide (HPMA) copolymers containing coiled-coil domains as side-chains (grafts) will be synthesized by copolymerization of HPMA with macromonomers containing coiled-coils. The design of coiled-coil grafts imposes an antiparallel heterodimer formation in the self-assembly process. We hypothesize that the antiparallel orientation of heterodimers will contribute to the homogeneity of the self-assembled hybrid hydrogels due to the unique interchain dimer formation and decreased steric hindrance of the polymer backbone on the """"""""in-register"""""""" alignment of heterodimers. Materials with tailor-made structures at the nanometer range will result from the proposed research. A theoretical model will be developed to assist in a rational design of the hybrid hydrogels. Experimental results will be analyzed using the model to provide feedback for the optimization of graft copolymer structure and of the self-assembly into hybrid hydrogels. The self-assembly of HPMA graft copolymers in the presence of encapsulated molecules will be evaluated in an attempt to develop new in-situ forming hybrid hydrogels for the delivery of proteins. The delivery system is suitable for a wide variety of biological molecules since the self-assembly occurs in aqueous media. The new hydrogels may find wide-ranging biomedical applications in drug delivery, biosensors, affinity separations, and nanoreactors. In addition, the possibility to join non-compatible materials, such as hydrophobic muscle mimics from liquid crystalline polymers and hydrogels, may open a new field of research.
| Yang, Jiyuan; Kope?ek, Jind?ich (2016) Design of smart HPMA copolymer-based nanomedicines. J Control Release 240:9-23 |
| Yang, Jiyuan; Kope?ek, Jind?ich (2015) POLYMERIC BIOMATERIALS AND NANOMEDICINES. J Drug Deliv Sci Technol 30:318-330 |
| Yang, Jiyuan; Kope?ek, Jind?ich (2014) Macromolecular therapeutics. J Control Release 190:288-303 |
| Kope?ek, Jind?ich (2013) Polymer-drug conjugates: origins, progress to date and future directions. Adv Drug Deliv Rev 65:49-59 |
| Wu, Kuangshi; Yang, Jiyuan; Liu, Jihua et al. (2012) Coiled-coil based drug-free macromolecular therapeutics: in vivo efficacy. J Control Release 157:126-31 |
| Johnson, Russell N; Kope?ková, Pavla; Kope?ek, Jind?ich (2012) Biological activity of anti-CD20 multivalent HPMA copolymer-Fab' conjugates. Biomacromolecules 13:727-35 |
| Kope?ek, Jind?ich; Yang, Jiyuan (2012) Smart self-assembled hybrid hydrogel biomaterials. Angew Chem Int Ed Engl 51:7396-417 |
| Wu, Larisa C; Yang, Jiyuan; Kope?ek, Jind?ich (2011) Hybrid hydrogels self-assembled from graft copolymers containing complementary ?-sheets as hydroxyapatite nucleation scaffolds. Biomaterials 32:5341-53 |
| Wu, Kuangshi; Liu, Jihua; Johnson, Russell N et al. (2010) Drug-free macromolecular therapeutics: induction of apoptosis by coiled-coil-mediated cross-linking of antigens on the cell surface. Angew Chem Int Ed Engl 49:1451-5 |
| Kopecek, Jindrich (2010) Biomaterials and drug delivery: past, present, and future. Mol Pharm 7:922-5 |
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