Dual gate-keeping and reversible on-off switching drug release for anti-cancer therapy with pH- and NIR light-responsive mesoporous silica-coated gold nanorods

This work reports the fabrication of AuNR@MSNs [i.e., gold nanorods (AuNRs) coated with mesoporous silica nanoshells (MSNs)] with independent sensitivities to pH and near-infrared (NIR) light for reversible on–off switching of drug release without premature drug leakage. The fabrication involves the incorporation of lauric acid (LA) as a thermosensitive gatekeeper, followed by the coating of tannic acid (TA) layers as a pH-sensitive gatekeeper. The protonation–deprotonation of the TA layers according to change in pH can result in their swelling–deswelling to induce pH-sensitive drug release, while the solid–liquid phase transition of LA by NIR light-induced heat generation in AuNRs enables the NIR light-controlled release of preloaded drug molecules. The interplay between these dual gatekeepers allows the release of pre-loaded drug from the AuNR@MSN-LA@TAs (i.e., AuNR@MSNs incorporating LA and TA) only at acidic conditions under NIR light irradiation, without premature drug leakage under inactive conditions (neutral pH or no NIR light). Moreover, the reversibility of the gatekeepers can make an on–off mannered drug release. Benefiting from the capability of the gatekeepers to induce pH-/temperature-sensitive release, along with the photothermal ability of AuNRs, the AuNR@MSN-LA@TAs can exhibit a satisfactory anticancer performance without undesired drug leakage.