Responsive Supramolecular Devices Assembled from Pillar[5]arene Nanogate and Mesoporous Silica for Cargo Release

In this work, cationic switchable pillar[5]arene nanogates that bear an imidazolium scaffold (MIP5(+)) were constructed, and these nanogates were used to electrostatically interact with negatively charged spherical mesoporous silica nanoparticles (96.0 +/- 1.0 nm) and rod-shaped silica particles (391.0 +/- 0.2 nm in length and 219 in width), which are both functionalized with carboxypropyl groups. The nanochannels of silica-based materials were used as containers to store the anticancer drug doxorubicin (DXR) trapped by the nanogate. Under physiological conditions (pH = 7.4), DXR molecules were firmly trapped in the nanochannels of the spherical and rod-shaped containers without any premature release, demonstrating that the nanogate was efficient in sealing the nanopores. Under acidic conditions (pH = 4.5), the carboxypropyl groups were protonated, and the electrostatic interactions between the containers and the nanogates were disrupted, releasing the drug. In vitro studies were performed to explore the differences between N-methylimidazolium-pillar[5]arene nanogate mounted on DXR-loaded spherical and rod-shaped containers and the resulting cytotoxicity effect against human breast adenocarcinoma cells and cellular uptake. A higher cytotoxicity effect and better cellular uptake were detected for the nanogate on DXR-loaded rod-shaped silica containers. Additionally, this device presents a lower uptake rate by nontumor cells than that of free DXR. Therefore, our findings indicate that the rod shape of mesoporous silica in nanogated devices is important due to the cytotoxicity effect and cellular uptake and should be further explored in drug delivery systems.