Janus gold nanostar–mesoporous silica nanoparticle (AuNSt–MSNP) nanodevices able to release an entrapped payload upon irradiation with near infrared (NIR) light were prepared and characterized. The AuNSt surface was functionalized with a thiolated photolabile molecule (5), whereas the mesoporous silica face was loaded with a model drug (doxorubicin) and capped with proton‐responsive benzimidazole‐β‐cyclodextrin supramolecular gatekeepers (N 1). Upon irradiation with NIR‐light, the photolabile compound5photodissociated, resulting in the formation of succinic acid, which induced the opening of the gatekeeper and cargo delivery. In the overall mechanism, the gold surface acts as a photochemical transducer capable of transforming the NIR‐light input into a chemical messenger (succinic acid) that opens the supramolecular nanovalve. The prepared hybrid nanoparticles were non‐cytotoxic to HeLa cells, until they were irradiated with a NIR laser, which led to intracellular doxorubicin release and hyperthermia. This induced a remarkable reduction in HeLa cells viability.

NIR‐light irradiationof a Janus gold nanostar–mesoporous silica nanoparticle nanodevice induced succinic acid generation and doxorubicin release due to the dethreading of a supramolecular nanovalve.