Polymer chemistry is an essential connection between organic chemistry, chemical biology and materials science. This living world has presented us many examples of the usages of polymers, such as delivery vehicle, recognition unit, support materials, information storage,5 and so on. Scientists have been trying to create synthetic polymers that can mimic such functionalities and bring widespread applications in different fields. For all synthetic polymers, their properties and potential applications are all based on their chemical nature. This is especially true for synthetic polymeric materials for bio-related applications, because of the delicate and complicated working environments and mechanisms of such biomaterials. Consequently, more facile and delicate controls over the polymers' chemical nature are in great demand, and bottom-up strategy for the synthesis of smart polymers have been more common in the recent decades.;In this thesis paper, multiple bottom-up syntheses of useful polymeric materials are recorded. In the first part of the thesis, a new approach to prepare functional organic nanoparticles (ONPs) from linear polymers is described. The nanoparticles were obtained by consecutive ring-opening metathesis polymerization and ring-closing metathesis. This flexible and mild synthesis allowed preparation of organic- and aqueous-soluble particles with controllable size and narrow molecular weight distributions. The use of functional monomer(s) and/or chain-transfer agents had led to controllable synthesis of nanoparticles containing single, dual, or multiple reactive functional groups. Such non-toxic ONPs with many controllable parameters could be used to study the effect of surface functional groups on the cellular uptake of corresponding nanoparticles. In addition, dye-functionalized ONPs could serve as water-soluble fluorophores with highly enhanced photostability. Moreover, other functional materials such as DNAs could be conjugated onto the ONPs, bringing in new hybrid materials with applications. The ONPs and ONP-DNA conjugates could also serve as templates for the synthesis of metal nanoparticles, providing a direct and facile synthetic route for functional metal nanoparticles.;In the second part of this paper, major focus is set on a polymeric approach to enhance the efficacy of toxic r(CUG)n-binding compounds for potential Myotonic Dystrophy Type I (DM1) treatment. Also using a bottom-up living polymerization strategy, cell-penetrating polymers bearing active r(CUG)n binding ligands are prepared. The synthetic polypeptide binder was shown to have excellent performance in both molecular and cell studies, giving much enhanced binding to the toxic RNA. The ligand-polypeptide conjugates could successfully disperse ribonuclear foci caused by r(CUG)n-MBNL1 complex, and could fully reverse the mis-splicing of Insulin receptor (IR) mRNAs in the model cells. In addition, potentially due to the polymer-mediated catalytic degradation, r(CUG)n level in the model cells could be greatly reduce by low concentration treatment of the ligand-bearing polymeric material.
展开▼
