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

Area of Science:

• Supramolecular Chemistry
• Nanotechnology
• Materials Science

Background:

• Pillararene-based molecular machines offer diverse applications.
• Mesoporous silica nanoparticles (MSNs) are widely used for drug delivery.
• Developing advanced nanocarriers with controlled release mechanisms is crucial for effective therapeutics.

Purpose of the Study:

• To synthesize phosphonated pillar[5]arenes (PPA[5]) for constructing novel supramolecular nanovalves.
• To investigate the host-guest interactions for enhanced drug encapsulation and controlled release.
• To evaluate the potential of PPA[5]-based nanovalves, especially when integrated with gold nanorods (GNRs), for tumor photothermo-chemotherapy.

Main Methods:

• Synthesis of phosphonated pillar[5]arenes (PPA[5]).
• Functionalization of mesoporous silica nanoparticles (MSNs) with choline and pyridinium moieties.
• Construction of supramolecular nanovalves by encircling functionalized MSNs with PPA[5].
• Evaluation of drug release triggered by low pH, Zn²⁺, and competitive agents.
• Assessment of enhanced drug delivery and antitumor efficacy using GNR-embedded MSNs (GNR@MSNs) under near-infrared (NIR) light irradiation.

Main Results:

• Novel supramolecular nanovalves were successfully constructed using PPA[5] and functionalized MSNs.
• PPA[5] demonstrated high binding affinity to quaternary ammonium stalks via ion pairing, minimizing premature drug release.
• Controlled drug release was achieved, and release efficiency was significantly enhanced in GNR@MSNs under NIR light.
• Synergistic photothermo-chemotherapy using PPA[5]-valved GNR@MSNs showed enhanced antitumor efficacy.

Conclusions:

• Phosphonated pillar[5]arenes are effective in constructing robust supramolecular nanovalves for drug delivery.
• The ion-pairing interaction between PPA[5] and quaternary ammonium moieties provides a stable yet triggerable drug delivery system.
• The PPA[5]-valved GNR@MSN system holds significant promise for advanced tumor photothermo-chemotherapy applications.