Ultrafast photochemistry produces superbright short-wave infrared dots for low-dose in vivo imaging

12 p.-5 fig.Optical probes operating in the second near-infrared window (NIR-II, 1,000-1,700 nm), where tissues are highly transparent, have expanded the applicability of fluorescence in the biomedical field. NIR-II fluorescence enables deep-tissue imaging with micrometric resolution in animal models, but is limited by the low brightness of NIR-II probes, which prevents imaging at low excitation intensities and fluorophore concentrations. Here, we present a new generation of probes (Ag2S superdots) derived from chemically synthesized Ag2S dots, on which a protective shell is grown by femtosecond laser irradiation. This shell reduces the structural defects, causing an 80-fold enhancement of the quantum yield. PEGylated Ag2S superdots enable deep-tissue in vivo imaging at low excitation intensities (<10 mW cm-2) and doses (<0.5 mg kg-1), emerging as unrivaled contrast agents for NIR-II preclinical bioimaging. These results establish an approach for developing superbright NIR-II contrast agents based on the synergy between chemical synthesis and ultrafast laser processing.Authors thank Dr A. Benayas (CICECO, U. Aveiro, Portugal), Prof G. Lifante and Prof J. García Sole (UAM) for helpful discussions. This work has been founded by Ministerio de Economı́a y Competitividad-MINECO (MAT2017-83111R and MAT2016-75362-C3-1-R) and the Comunidad de Madrid (B2017/BMD-3867 RENIM-CM) co-financed by European Structural and Investment Fund. D.M.-G. thanks UCM-Santander for a predoctoral contract (CT17/17-CT18/17). We thank the staff at the ICTS-National Centre for Electron Microscopy at the UCM for the help in the electron microscopy studies and C.M. at the beamline BL22-CLAESS of the Spanish synchrotron ALBA for his help in the XANES experiments. We also thank J.G.I at the Ultrafast Laser Laboratory at UCM for his help and fruitful discussion. Y.S. acknowledges the support from the China Scholarship Council (CSC File No. 201806870023). Additional funding was provided by the European Commission Horizon 2020 project NanoTBTech, the Fundación para la Investigación Biomédica del Hospital Universitario Ramón y Cajal project IMP18_38 (2018/0265). Ajoy K. Kar and Mark D. Mackenzie acknowledge support from the UK Engineering and Physical Sciences Research Council (Project CHAMP, EP/M015130/1). C. Jacinto thanks the financial support of the Brazilian agencies: CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) through the grants: Projeto Universal Nr. 431736/2018-9 and Scholarship in Research Productivity 1C under the Nr. 304967/20181; FINEP (Financiadora de Estudos e Projetos) through the grants INFRAPESQ-11 and INFRAPESQ-12; FAPEAL (Fundação de Amparo à Pesquisa do Estado de Alagoas) grant Nr. 1209/2016. H. D. A. Santos was supported by a graduate studentship from CNPq and by a sandwich doctoral program (PDSE-CAPES) developed at Universidad Autonoma de Madrid, Spain, Project Nr. 88881/2016-01.Peer reviewe