Smart drug delivery systems based on specifically-designed macromolecules and inorganic colloids

In the past few decades, various hybrid nano-vehicles have been developed as new drug delivery systems (DDS), in which inorganic and organic components are integrated within a nano-object. An ideal DDS should satisfy the conflicting requirements for high stability in extracellular fluid, so that it maintains its integrity during the in vivo circulation; however, it becomes labile upon the activation of internal or external stimuli after targeting to the disease sites, allowing the triggered release of therapeutic agents. The aim of this thesis was to build different hybrid nano-vehicles, explore the possibility to manipulate the release behaviors and evaluate their potential biomedical application. The first part presents an original work on reversibly-crosslinked nanogels based on poly(vinyl alcohol)-b-poly (Nvinylcaprolactam) copolymers. The second part is devoted to stimuli-responsive hybrid nanovehicles, composed of inorganic cores, e.g. maghemite nanoparticles or gold nanorods, and a stimuli-responsive polymer corona, e.g. poly(vinyl alcohol)-b-poly(acrylic acid) or poly(ethyl glycol)-b-poly(N-vinylcaprolactam). The third part focuses on core-shell nanoparticles made of a maghemite core and a mesoporous silica shell, while phase-changed molecules, e.g. 1-tetradecanol with melting temperature of 39 °C, were introduced as gatekeepers to regulate the release behaviors. These different nanostructures were developed as DDS to accommodate cargo molecules, and the triggered cargo release upon variation in pH or temperature, activation of reductive agent or presence of glucose was explored. Moreover, remote stimuli, e.g. alternating magnetic field or near infrared light, were also applied to trigger the release. Studies on cytotoxicity, cellular uptake and in vitro triggered release with cell culture are also described.