Applications of a Unique Nopoldiol-Benzoxaborolate Cross-link in Biomaterials

Abstract

A novel nopoldiol-benzoxaborolate cross-link formed by a bioorthogonal click reaction between nopoldiol- and benzoxaborole-based components was developed for the preparation of biomaterials such as hydrogels and nanogels. In contrast to the traditional boronic ester-based cross-links, this hydrolytically stable, acid-resistant, and bioorthogonal cross-link provides an innovative strategy for the preparation of highly stable and widely applicable biomaterials. In Chapter 2, the application of this chemistry towards an in situ forming, self-healing, and bioorthogonal hydrogel is described. The resulting hydrogel shows a number of advantages, such as fast gelation process, self-healing within a wide range of pH (8.5–1.5), polyol-resistant properties, and reactive oxygen species (ROS)-responsive properties. In addition, the biomedical applications of this hydrogel system were demonstrated by pH-responsive release of an anti-cancer drug (doxorubicin) and 3D encapsulation of live cells. Furthermore, efforts on the development of a nanogel-based drug carrier for the encapsulation of another anti-cancer drug, capecitabine (CAPE), are presented in Chapter 3. Nopoldiol-benzoxaborolate cross-links were included in nanogels to produce a more stable drug carrier with ROS-responsive properties. Then, the application of a polymer–drug covalent binding strategy was evaluated in the conjugation of benzoxaborole-based polymer and CAPE through boronic ester formation. Although the nanogels demonstrated pH- and ROS- controlled release of CAPE, a more efficient encapsulation method needs to be explored further.