doi:10.1016/j.jcis.2021.09.064engAlejo, TeresaSebastian, VictorMendoza, GraciaArruebo, ManuelHybrid thermoresponsive nanoparticles containing drug nanocrystals for NIR-triggered remote releaseART-2022-128054The on-demand administration of anaesthetic drugs can be a promising alternative for chronic pain management. To further improve the efficacy of drug delivery vectors, high drug loadings combined with a spatiotemporal control on the release can not only relief the pain according to patient''s needs, but also improve the drawbacks of conventional burst release delivery systems. In this study, a hybrid nanomaterial was developed by loading bupivacaine nanocrystals (BNCs) into oligo(ethylene glycol) methyl ether methacrylate (OEGMA)-based thermoresponsive nanogels and coupling them to NIR-absorbing biodegradable copper sulphide nanoparticles (CuS NPs). Those CuS NPs were surface modified with polyelectrolytes using layer-by-layer techniques to be efficiently attached to the surface of nanogels by means of supramolecular interactions. The encapsulation of bupivacaine in the form of nanocrystals allowed to achieve CuS@BNC-nanogels having drug loadings as high as 65.5 wt%. The nanocrystals acted as longlasting drug reservoirs, leading to an elevated localized drug content, which was useful for their application in prolonged pain relief. The CuS@BNC-nanogels exhibited favorable photothermal transducing properties upon NIR-light irradiation. The photothermal effect granted by the CuS NPs triggered the nano-crystallized drug release to be boosted by the collapse of the thermoresponsive nanogels upon heating. Remote control was achieved for on-demand release at a specific time and place, indicating their potential use as an externally activated triggerable drug-delivery system. Furthermore, cell viability tests and flow cytometry analysis were performed showing satisfactory cytocompatibility in the dose-ranging study having a subcytotoxic concentration of 0.05 mg/mL for CuS@BNC-nanogels. This remotely activated nanoplatform is a promising strategy for long-lasting controlled analgesia and a potential alternative for clinical pain management. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license2022http://zaguan.unizar.es/record/11275510.1016/j.jcis.2021.09.064http://zaguan.unizar.es/record/112755oai:zaguan.unizar.es:112755info:eu-repo/grantAgreement/EUR/ERC-2013-CoG-614715info:eu-repo/grantAgreement/ES/ISCIII-IIS/MS19-00092info:eu-repo/grantAgreement/ES/MCIU/RTI2018-099019-A-I00Journal of Colloid and Interface Science 607, Part 2 (2022), 1466-1477by-nc-ndhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccess