Thermoresponsive “Click” Core@shell Poly(cyanoacrylate) Nanoparticles for Controlled Chemotherapy Release

High Resolution Image Download MS PowerPoint Slide Carriers that release cargo molecules over extended times under physiological conditions following a predictable delay, but which are also stable/have shelf life without release, are needed for chemotherapy. We report the preparation and characterization of poly(cyanoacrylate) core@shell nanoparticles as burst-free thermoresponsive drug delivery systems. Extraordinarily monodisperse poly( n -butyl cyanoacrylate)@poly(allyl cyanoacrylate) nanoparticles were prepared with control over the core size and shell thicknesses. Phenolphthalein, a model dye, or the chemotherapy drug daunorubicin was loaded into the cores during the synthesis without altering the particle size or colloidal stability. Following shell formation, transformation of accessible surface allyl groups in the shells to epoxide functionalities (i) enabled subsequent grafting with poly(ethylene glycol) for extending blood circulation time, or with thermoresponsive polymers to provide reversible temperature-dependent aggregation/colloidal destabilization, and (ii) suppressed diffusive processes, limiting the release at room temperature and providing an unprecedented release-free induction time with subsequent accelerated release at physiological temperature. The potential of core@shell poly(cyanoacrylate) NPs for stimulated release applications for multiple types of cargo is discussed.