Owing to the overuse of rough articular cartilage, it increases the friction of joint and further leads to inflammation in joint cavities. However, the pathological changes also bring a new opportunity to achieve the treatment of osteoarthritis (OA). The increasing friction from damaged articular cartilage can convert more mechanical energy to heat. The higher localized temperature can reduce supramolecular interactions in general. Therefore, friction becomes another new activation to operate nanovalve systems for the targeting treatment of OA. Here, we designed and prepared a friction-induced nanovalve system constructed with b-cyclodextrins (b-CD)-modified mesoporous silica nanoparticles (MSN). Besides, a copolymer containing two components - guest molecules (adamantane, AD) and poly(2methacryloyloxyethyl phosphorylcholine) (PMPC) - has been self-assembled on the surface of b-CDmodified MSN (MSN-CD) by supramolecular host-guest interactions. In this design, the charged PMPC on the MSN surface can form a dense hydration layer by ion-dipole interactions, switch the friction from surfaces to water molecules to achieve hydration lubrication, and sharply reduce the coefficient of friction (COF). Besides, the higher localized temperature from the mechanical conversion can weaken the supramolecular host-guest interactions and turn on the nanovalves to accomplish the targeted release near rough articular cartilage of OA. Even when PMPC is peeled off, the hydrophilic surface of b-CD on MSN surface can still perform the acceptable lubricating properties. The following testings of cytotoxicity by CCK-8 and live/dead staining indicated the excellent biocompatibility. Further analysis of protein expression levels has also shown the potential application in OA. (c) 2022 Elsevier Ltd. All rights reserved.