A reversible light-operated nanovalve on mesoporous silica nanoparticles

Abstract

Two azobenzene α-cyclodextrin based nanovalves are designed, synthesized and assembled on mesoporous silica nanoparticles. Under aqueous conditions, the cyclodextrin cap is tightly bound to the azobenzene moiety and capable of holding back loaded cargo molecules. Upon irradiation with a near-UV light laser, trans to cis-photoisomerization of azobenzene initiates a dethreading process, which causes the cyclodextrin cap to unbind followed by the release of cargo. The addition of a bulky stopper to the end of the stalk allows this design to be reversible; complete dethreading of cyclodextrin as a result of unbinding with azobenzene is prevented as a consequence of steric interference. As a result, thermal relaxation of cis- to trans-azobenzene allows for the rebinding of cyclodextrin and resealing of the nanopores, a process which entraps the remaining cargo. Two stalks were designed with different lengths and tested with alizarin red S and propidium iodide. No cargo release was observed prior to light irradiation, and the system was capable of multiuse. On/off control was also demonstrated by monitoring the release of cargo when the light stimulus was applied and removed, respectively.

Fig. 1

Schematic overview of the synthesis of FRS1-MSN and EXT2-MSN; p-nitrobenzoic acid is reacted with glucose to give 1. Reaction with N-hydroxysucciminide yields 2. Monosubstitution of 2 with one equivalent of 2a or 2b yields 3a or 3b, respectively. Complexation with α-cyclodextrin forms the α-cyclodextrin/azobenzenepseudorotaxanes FRS1-NHS or FRS1-NHS. Reaction of the pseudorotaxanes with APTES-MSNs yields FRS1- MSN or EXT2-MSN.

Fig. 2

(a) Size illustration of various cargo molecules in reference to (b) azobenzene stalks FRS1-MSN and EXT2-MSN. Because of the shorter stalk length, FRS1-MSN is limited to loading cargo molecules < 2 nm. Hoechst 33342 and propidium iodide dyes remain excluded from FRS1-MSN as a result of their size. However, EXT2-MSN is observed to load all three of the listed fluorophores. (c) Schematic illustration of the fully assembled rotaxane nanovalve and operation. (1) After synthesis, the nanovalves are suspended in an organic solvent, which destabilizes hydrophobic interactions between the α-cyclodextrin and azobenzene moiety and allows for cargo loading. (2) Upon solvent exchange to water, rebinding of the cyclodextrin to azobenzene seals in the loaded cargo. (3) Irradiation with light induces isomerization to cis-azobenzene, forcing cyclodextrin to move to the end of the stalk, and allowing cargo to release. (4) Upon removal of the light stimulus, thermal relaxation of cis-azobenzene to its more stable trans isomer allows rebinding of the cyclodextrin and seals in the remaining cargo.

Fig. 3

(a) Time resolved fluorescence spectra showing the light activated (403 nm) release of alizarin red S (ARS) dye from FRS1-MSN. Initial loading of the particles results in minimal release prior to irradiation (trace 1). When the pump beam is activated, ARS fluorescence steadily increases in the supernatant. After the release is complete, FRS1-MSN were reloaded with ARS and washed before reinitiating cargo release. Trace 2 shows these reloaded FRS1-MSN releases ARS equally as well. An identical experiment was performed on the EXT2-MSN system (b) using PI dye instead. EXT2-MSN exhibits the same behavior as FRS1-MSN with the larger fluorophore. These results demonstrate that the full rotaxane systems are reversible, reusable and can bedesigned to release different sized cargos.

Fig. 4

Time resolved fluorescence spectra demonstrating the on-off properties of FRS1-MSN. (a) Stimuli-response release profile; light stimuli causes the release of the ARS. When the light is turned off, the fluorescence intensity levels out until the stimulus is reapplied. (b) Release from the particles modified by 3a rather than FRS1-NHS. The stalk, lacking the cyclodextrin nanocap, shows a continuous release of ARS without application of light. Therefore, the α-cyclodextrin is required to form the complete nanovalve system and prevent leakage of cargo.