Self-Immolative Polymers for Nanoparticles with Unique Degradation Profiles in Biomedical Applications
Résumé
Self-Immolative polymers (SIPs) are new class of polymers able to translate an external stimulus into a depolymerization reaction [1], this unique feature makes them suitable for applications in which temporary structures are needed, such as nanoparticles for drug delivery.[2] The incorporation of SIPs in such systems can lead to overcome important barriers in the field of drug delivery, such as passive release, inertia, interferences between the stimulus and the physiological parameters (T°, pH) etc. This work aims to extend SIPs domain from chemistry to macromolecular engineering, in order to design SIP-based amphiphilic bloc copolymers, and then stimuli-responsive nanoparticles for controlled and on-demand drug release. UV- and NIR-sensitive groups were combined with caprolactone rings in order to make ROP polymerizable monomers. Then the polymerization of these monomers was initiated by polyethylene glycol to make diblock and triblock amphiphilic copolymers. Thanks to their amphiphilic character, the copolymers make self-assemblies in solvents and encapsulate drug models. Since the copolymers contain SIP segments, the obtained self-assemblies can be dissociated by irradiation. Copolymers with different chain lengths and different PEG/SIP ratios were synthesized in this work. The self-assembling behavior of the copolymers was demonstrated. The depolymerization of the copolymers as well as the dissociation of the self-assemblies were monitored by different techniques. The on-demand and controlled release of Nile Red from these self-assemblies was demonstrated. By using SIP segments to make self-assemblies, it was possible to control quantitatively the kinetics of the degradation of the copolymers. As consequence, the dissociation of the nanoparticles could be triggered, and the dissociation kinetics could be controlled. The Nile Red was successfully used as model to demonstrate the possibility to trigger and control the drug-release from the self-assemblies