Synthesis of functional biomaterials from natural building blocks

This dissertation describes the syntheses of functional polymeric biomaterials from natural monomeric building blocks for application specific to vectors for gene delivery. Chapter 1 of this dissertation introduces and discusses the various chemical and biological challenges of synthetic polymeric vectors for gene delivery. In particular, Chapter 1 examines various barriers at the cellular level for efficient gene transfer. In addition, chemical strategies to overcome such biological barriers are also discussed. Finally, a variety of synthetic vectors with various design and chemical diversities are presented. In particular, incorporation of an environmentally responsive bond into synthetic vectors is introduced as one of the main design characteristics necessary for overcoming multiple biological challenges. Overall, the introductory chapter attempts to illustrate the sensitive balances and complexities observed in the field of gene delivery. Chapter 2 of this dissertation describes the influence of structural modifications on saccharide-peptide hybrid copolymer (SPHC) as a synthetic vector for plasmid DNA and short interfering RNA delivery. SPHCs with various cationic charge densities, buffering capabilities, and cross-linking densities were prepared and consequences of these modifications on SPHCs are discussed. Chapter 3 of this dissertation describes the surfactant-free synthesis of bioreducible and biocompatible cationic nanogels intended for siRNA delivery. Nanogels were prepared by cross-linking the linear polymeric precursors in combination with polar and non-polar organic solvents without the addition of surfactants. The presence of amine side chains off the polymer backbone were determined to be crucial for efficient siRNA complexation. Our results (size, stability, environment responsiveness, and toxicity profile) clearly reveal the potential of this nanogel to be applied as a nano-colloidal drug carrier. Chapter 4 describes an efficient living ring-opening polymerization (ROP) of a permethoxylated-caprolactone [(OMe)CL] catalyzed by yttrium(III) isopropoxide for development of degradable protein-resistant polymers [P(OMe)CL]. The lactone monomer was efficiently prepared from a reduced sugar, D-dulcitol. A series of block copolymers consisting of permethoxylated lactone and epsilon-caprolactone [P(OMe)CL-b-PCL] were synthesized and characterized. Finally, surface plasmon resonance (SPR) sensorgrams demonstrated that both P(OMe)CL and the P(OMe)CL-b-PCL block copolymers exhibit excellent resistance to protein adsorption.