1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 z Materials Science inc. Nanomaterials & Polymers From Concentrated Dispersion to Solid β-Cyclodextrin Polymer-Capped Silver Nanoparticle Formulation: A Trojan Horse Against Escherichia coli Rudy Martin-Trasanco,* [a] Giovanna Anziani-Ostuni, [b] Hilda Esperanza Esparza-Ponce, [c] Pedro Ortiz, [d] María E. Montero-Cabrera, [c] Diego P. Oyarzún, [a] César Zúñiga, [f] José Manuel Pérez-Donoso, [b] Guadalupe del C. Pizarro, [e] and Ramiro Arratia-Pérez [a] Preparation of concentrated silver nanoparticles in water remains a challenge today. The intrinsic reactivity of silver, as well as the high surface energy of nanoparticles, make it difficult to handle them without altering their pristine proper- ties. Herein, we report the preparation of concentrated silver nanoparticles (AgNPs) dispersion (2 mM; 1.5⋅10 15 NPs/mL) by reducing Ag + in-situ of a β-cyclodextrin-epichlorohydrin poly- mer (βCDP) as a capping agent. The prepared nanoparticles (AgNPs@βCDP) with a Surface Plasmon Resonance band at 396 nm, and a hydrodynamic diameter of 21.4 � 1.8 nm, retained both features after being precipitated and re- dispersed in water. The AgNPs core had a spherical morphol- ogy, with a 12.7 � 1.5 nm diameter in size, as determined by TEM. The AgNPs@βCDP showed outstanding bactericidal properties against Escherichia coli (MIC = 0.37 nM), one of the lowest ever achieved for silver nanoparticles. We suggest that the polymer acts as a Trojan horse with AgNPs as payload. Introduction Over the last three decades, an explosion in the synthesis of noble metal nanoparticles (MNPs) has occurred because of their unique physical, chemical, and biological properties. [1,2] Among them, the preparation of silver nanoparticles (AgNPs) has been widely addressed due to the biomedical properties of this element. As bactericidal, silver is employed in dental works, catheters, coating stainless steel materials, and burn injuries, among many others. [3,4] Additionally, the antiviral and anti- cancer effect of AgNP has been recently reported. [5–8] AgNPs have a large active surface area that produces an efficient interaction with cells and tissues. The high surface area of AgNPs is, in turn, a problem for the chemical stability of these systems because they are easily oxidized, tend to aggregate and consequently precipitate. To overcome this drawback, the nanoparticle surface should be passivized, or protected by a capping agent. [9] Preparation of AgNPs can be achieved by chemical, physical or biological methods. [10] For biomedical applications, the chemical methods based on the synthesis in water are the most desirable ones. In water, AgNPs are commonly prepared by chemical methods based on the reduction of a silver salt with a reducing agent. [11] Nevertheless, this methodology is restricted to the preparation of AgNPs at a low concentration (< 10 13 NPs/mL), a drawback considering economic feasibility. [12] A few methods are related to the synthesis of highly concentrated AgNPs dispersions (� 10 15 NPs/mL) but, due to the cytotoxicity of the chemicals employed, none of them are feasible for biomedical applications. [11,13–16] Pointing to the preparation of AgNPs with biocompatible compounds, several occurring natural products, like polysaccharides, have been used as reducing and stabilizing agents. Nevertheless, the concentrations of nanoparticles do not exceed the value of 10 13 NPs/mL by any of the described methods. [17–20] β-Cyclodextrin (βCD) has been used in the preparation of AgNPs. This natural oligosaccharide, which additionally forms inclusion complexes with a wide variety of drugs, can act as a capping and reducing agent and serve to control the size and shape of the AgNPs.[ 21–26] Additionally, cyclodextrin it-self and its derivatives have been proved as bactericidal. [27] The bactericidal properties of AgNPs, combined with the capability of βCD to form inclusion complexes, are promising [a] Dr. R. Martin-Trasanco, Dr. D. P. Oyarzún, Prof. Dr. Ramiro Arratia-Pérez Center for Applied Nanosciences (CANS), Universidad Andres Bello, Av. República 275, Santiago 8370146, Chile Tel.: + 56 9 5936 2441 E-mail: ruquim@gmail.com [b] G. Anziani-Ostuni, Prof. Dr. J. M. Pérez-Donoso Laboratorio de Bionanotecnología y Microbiología, Centro de Bioinformá- tica y Biología Integrativa (CBIB), Facultad de Ciencias Biológicas, Universidad Andres Bello, Av. República 239, Santiago de Chile [c] Dr. H. E. Esparza-Ponce, Prof. Dr. M. E. Montero-Cabrera Centro de Investigación en Materiales Avanzados S.C, Ave. Miguel de Cervantes 120, Complejo Industrial Chihuahua, Chihuahua, México [d] Dr. P. Ortiz Departamento de Química Inorgánica, Facultad de Química, Pontificia Universidad Catolica de Chile, Avenida Vicuña Mackenna, 4860, Santiago 7820436, Chile [e] Prof. Dr. G. d. C. Pizarro Departamento de Química, Universidad Tecnológica Metropolitana, J. P. Alessandri 1242. Santiago, Chile [f] Dr. C. Zúñiga Instituto de Ciencias Naturales, Universidad de las Americas, Sede Providencia, Av. Manuel Montt 948, Santiago, Chile Supporting information for this article is available on the WWW under https://doi.org/10.1002/slct.201901406 Full Papers DOI: 10.1002/slct.201901406 10092 ChemistrySelect 2019, 4, 10092 – 10096 © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim