Dual gate-keeping and reversible on-off switching drug release for anticancer therapy with pH- and NIR light-responsive mesoporous silicacoated gold nanorods

This work reports the fabrication of AuNR@MSNs [i.e., gold nanorods (AuNRs) coated with mesoporoussilica nanoshells (MSNs)] with independent sensitivities to pH and near-infrared (NIR) light for reversibleon–off switching of drug release without premature drug leakage. The fabrication involves the incorporationof lauric acid (LA) as a thermosensitive gatekeeper, followed by the coating of tannic acid (TA) layersas a pH-sensitive gatekeeper. The protonation–deprotonation of the TA layers according to change inpH can result in their swelling–deswelling to induce pH-sensitive drug release, while the solid–liquidphase transition of LA by NIR light-induced heat generation in AuNRs enables the NIR light-controlledrelease of preloaded drug molecules. The interplay between these dual gatekeepers allows the releaseof pre-loaded drug from the AuNR@MSN-LA@TAs (i.e., AuNR@MSNs incorporating LA and TA) only atacidic 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 mannereddrug release. Benefiting from the capability of the gatekeepers to induce pH-/temperature-sensitiverelease, along with the photothermal ability of AuNRs, the AuNR@MSN-LA@TAs can exhibit a satisfactoryanticancer performance without undesired drug leakage. KCI Citation Count: 2