Polypeptide hybrid biomaterials developed from protein precursors - a novel strategy and biomedical applications

A convenient approach for the synthesis of narrowly dispersed protein based polypeptide copolymers (PbPs) of defined compositions is presented in this thesis. The controlled denaturation of the native proteins followed by an in situ stabilization with polyethylene(oxide) chains yielded PbPs with precisely defined backbone lengths as well as secondary structure elements. PbPs exhibited excellent solubility and stability in aqueous media, and insignificant cytotoxicity. Via a priori and a posteriori modification strategies, functionalized PbPs could be prepared with highly tunable properties, such as variable net charges, distinct hydrophobicity as well as varied self-assemble possibilities. Moreover, PbPs could further incorporate other functional moieties, serving as a highly versatile platform for broad applications. This thesis further describes the investigation on various biomedical applications of PbPs. Water soluble and biocompatible quantum dots (QDs) were prepared for bioimaging by coating the hydrophobic QDs with PbPs. These PbP-QDs were non-cytotoxic and notably stable in live cells. They have attractive pH responsive optical properties, which were attributed to conformational rearrangements of the peptide backbone on QDs surface. The QDs coated with positively charged PbP shell exhibited significant photo-responsiveness to DNA loading and were able to transfect plasmid DNA into mammalian cells. For anti-cancer drug delivery, drug molecules were loaded into PbPs micelles via hydrophobic interaction or covalent conjugation onto PbPs backbone. A highly defined multi-stimuli responsive core-shell system was achieved by conjugating doxorubicin with PbP backbone via hydrazone linker. In vitro and preliminary in vivo studies demonstrated the efficient drug delivery, controlled drug release, potent toxicity as well as beneficial passive targeting effect. MRI contrast agents were further introduced into this system to enable simultaneous imaging and therapy