Upconversion Nanoparticles DOI: 10.1002/anie.201403576 Versatile Synthetic Strategy for Coating Upconverting Nanoparticles with Polymer Shells through Localized Photopolymerization by Using the Particles as Internal Light Sources** Selim Beyazit, Serena Ambrosini, Nataliya Marchyk, Emilia Palo, Vishal Kale, Tero Soukka, Bernadette Tse Sum Bui,* and Karsten Haupt* In memory of Daniel Thomas Abstract: We present a straightforward and generic strategy for coating upconverting nanoparticles (UCPs) with polymer shells for their protection, functionalization, conjugation, and for biocompatibility. UCPs are attracting much attention for their potential use as fluorescent labels in biological applica- tions. However, they are hydrophobic and non-compatible with aqueous media; thus prior surface modification is essential. Our method uses the internal UV or visible light emitted from UCPs upon photoexcitation with near-infrared radiation, to locally photopolymerize a thin polymer shell around the UCPs. In this way, a large variety of monomers with different chemical functionalities can be incorporated. If required, a second layer can be added on top of the first. Our method can provide a large spectrum of surface functional groups rapidly and in one pot, hence offering a platform for the preparation of libraries of functional polymer-encapsulated UCPs for applications in bioassays, biosensing, optical imag- ing, and theranostics. Lanthanide-doped upconverting nanoparticles (UCPs) have attracted much attention because of their potential use as fluorescent labels in biological applications, such as bioimag- ing and bioassays. [1–3] UCPs are excited by low-energy near- infrared (NIR) or infrared light and emit UV or visible light in a process based on the sequential absorption of two or more photons, termed upconversion. [4, 5] NIR excitation has several advantages, as it has a high penetration depth in tissues and causes no photodamage to living cells. In contrast, with traditional fluorophores, such as organic dyes and semi- conductor quantum dots, which show downconversion fluo- rescence, the lower wavelengths of excitation induce high autofluorescence background in most biological materials and cause other drawbacks, such as photobleaching and poor chemical stability. [1, 2, 6] Moreover, UCPs possess low cytotox- icity, a narrow emission bandwidth, a large anti-Stokes shift, and high photostability, which make them ideal as lumines- cent labels. [7] Despite all these advantages, they have been limited in their bioapplication because of their hydrophobic nature and their nondispersity in aqueous media. Indeed, UCPs are preferentially synthesized in highly hydrophobic solvents (octadecene) with oleates as stabilizing ligands. [6, 8–10] Thus, in order to be applied in biological media, they have to be surface-modified, and additional functionalization is required to enable the covalent immobilization of biomole- cules, such as proteins, nucleotides, and antibodies. [1–4, 11] Currently, one of the most efficient and widely used strategies is to encapsulate the UCPs in a cross-linked silica shell by the Stçber or reverse-microemulsion method. [1, 4, 10–14] Although this strategy results in quite stable nanoparticles, post-treat- ment is not straightforward, and certain factors, such as the inability to remove the surfactants completely, might be a problem for in vivo applications. [9] Encapsulation with amphiphilic polymers, whereby the hydrophobic moiety of the polymer intercalates with the oleate ligands on the surface, and the hydrophilic part remains exposed to the solution, is another strategy and yields stable colloids. [15–17] To impart increased stability, the coated amphiphilic polymer shell can be further cross-linked, usually on its periph- ery. [9, 18–20] Neither method is very versatile or generally applicable. Herein, we report a facile and generic strategy to create a stable cross-linked polymer coating on UCPs, with a large choice of functional groups. The method consists of using the light generated by the visible or UV emissions of the UCPs when excited with a near-infrared (980 nm) light source to construct a thin polymer shell around the UCPs by photo- polymerization. Since the emission from the UCPs is weak as compared to direct light, polymerization is confined to the close proximity of the UCPs and thus yields core–shell particles (Figure 1). The polymer shell can be made hydro- philic or hydrophobic, charged or neutral, chemically reactive [*] S. Beyazit, Dr. S. Ambrosini, Dr. N. Marchyk, Dr. B. Tse Sum Bui, Prof. K. Haupt Compigne University of Technology CNRS Enzyme and Cell Engineering Laboratory Rue Roger Couttolenc, CS 60319, 60203 Compigne Cedex (France) E-mail: jeanne.tse-sum-bui@utc.fr karsten.haupt@utc.fr Homepage: http://www.utc.fr/mip E. Palo, V. Kale, Prof. T. Soukka University of Turku, Department of Biotechnology Tykistçkatu 6A, 20520 Turku (Finland) [**] We acknowledge financial support by the European Commission (Marie Curie Actions, projects IRMED: MCIAPP-2009-251307, NANODRUG: MCITN-2011-289554, and CHEBANA: MCITN-2010- 264772) and by the Region of Picardy (cofunding of equipment under CPER 2007-2013). We thank Frederic Nadaud and Caroline Boulnois for TEM measurements. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/anie.201403576. Angewandte Chemie 8919 Angew. Chem. Int. Ed. 2014, 53, 8919 –8923 # 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim