Phosphonated Pillar[5]arene-Valved Mesoporous Silica Drug Delivery Systems.

To explore the diversity and promising applications of pillararene-based molecular machines, phosphonated pillar[5]arenes (PPA[5]) were synthesized to construct novel supramolecular nanovalves for the first time, based on mesoporous silica nanoparticles (MSNs) functionalized with choline and pyridinium moieties, respectively. PPA[5] encircled the choline or pyridinium stalks to construct supramolecular nanovalves for encapsulation of drugs within the MSN pores. PPA[5] showed a high binding affinity for the quaternary ammonium stalks through the host-guest interactions primarily via ion pairing between the phosphonate and quaternary ammonium moieties, in comparison with carboxylated pillar[5]arene (CPA[5]), to minimize premature drug release. The specific ion pairing between the phosphonate and quaternary ammonium moieties was elaborated for the first time to construct supramolecular nanovalves. The supramolecular nanovalves were activated by low pH, Zn coordination, and competitive agents for controlled drug release, and release efficiency and antitumor efficacy were further enhanced when gold nanorod (GNR)-embedded MSNs (GNR@MSNs) were used instead under illumination of near-infrared (NIR) light, attributed to the synergistic effect of photothermo-chemotherapy. The constructed PPA[5]-valved GNR@MSN delivery system has promising applications in tumor photothermo-chemotherapy.