Temperature-switched controlled release nanosystems based on molecular recognition and polymer phase transition

摘要

Environmental stimuli-responsive nanosystems that can release their encapsulated or loaded substances in spatial-, temporal- and dosage-controlled fashions have attracted tremendous attention, especially from the field of nanomedicine. In this work, a novel temperature-switched controlled release nanosystem based on the molecular recognition of beta-cyclodextrin (beta-CD) and thermosensitivity based on the phase transition of poly(N-isopropylacrylamide) (PNIPAM) is developed. This smart nanosystem consists of magnetic Fe3O4 colloidal nanocrystal clusters (MCNCs) core grafted with linear PNIPAM chains attached to numerous beta-CD units, (denoted as Fe3O4@ PNG-CD). beta-CD units act as containers for the loading of hydrophobic model drugs, PNIPAM chains serve as intelligent "microvalves" for controlling the release of loaded model drugs, and MCNCs core can achieve a "site-specific targeting" function. The gating mechanism involves that temperature can significantly affect the association constants of beta-CD toward model drug molecules in beta-CD modified PNIPAM chains. The resultant Fe3O4@ PNG-CD nanoparticles have excellent thermo-reversible adsorption/desorption properties for the loaded model drug 8-anilino-1-naphthalenesulfonic acid ammonium salt (ANS), and demonstrate a positive temperature "on-off" release fashion. By simply changing the temperature, the delivery rate can be effectively controlled. At temperature above the lower critical solution temperature (LCST) of the grafted PNG-CD chains (open gate), the delivery rate of ANS is fast, but very slow at temperature below the LCST (closed gate). These multifunctional nanoparticles provide a new mode for designing and engineering intelligent controlled release nanosystems.