Joyce, P.Allen, C.J.Alonso, M.J.Ashford, M.Bradbury, M.S.Germain, M.Kavallaris, M.Langer, R.Lammers, T.Peracchia, M.T.Popat, A.Prestidge, C.A.Rijcken, C.J.F.Sarmento, B.Schmid, R.B.Schroeder, A.Subramaniam, S.Thorn, C.R.Whitehead, K.A.Zhao, C.X.et al.2025-01-232025-01-232024Nature Nanotechnology, 2024; 19(11):1597-16111748-33871748-3387https://hdl.handle.net/2440/143616Nanomedicines have created a paradigm shift in healthcare. Yet fundamental barriers still exist that prevent or delay the clinical translation of nanomedicines. Critical hurdles inhibiting clinical success include poor understanding of nanomedicines’ physicochemical properties, limited exposure in the cell or tissue of interest, poor reproducibility of preclinical outcomes in clinical trials, and biocompatibility concerns. Barriers that delay translation include industrial scale-up or scale-down and good manufacturing practices, funding and navigating the regulatory environment. Here we propose the DELIVER framework comprising the core principles to be realized during preclinical development to promote clinical investigation of nanomedicines. The proposed framework comes with design, experimental, manufacturing, preclinical, clinical, regulatory and business considerations, which we recommend investigators to carefully review during early-stage nanomedicine design and development to mitigate risk and enable timely clinical success. By reducing development time and clinical trial failure, it is envisaged that this framework will help accelerate the clinical translation and maximize the impact of nanomedicines.en© Springer Nature Limited 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.Drug delivery; NanoparticlesAnimalsHumansDrug Delivery SystemsNanostructuresNanomedicineClinical Trials as TopicTranslational Research, BiomedicalJournal article10.1038/s41565-024-01754-7708804