Photoresponsive Nanoparticles DOI: 10.1002/anie.201305253 A UV-Blocking Polymer Shell Prevents One-Photon Photoreactions While Allowing Multi-Photon Processes in Encapsulated Upconverting Nanoparticles** Tuoqi Wu, Madeleine Barker, KhaledM. Arafeh, John-Christopher Boyer, Carl-Johan Carling, and Neil R. Branda* The use of low-energy two-photon excitation to provide information about where and when non-invasive photore- lease [1–5] and photodynamic therapy (PDT) [6–9] processes occur avoids the need for high-energy UV or visible light. Although this is an effective way to activate photoresponsive agents while minimizing damage to cells and increasing penetration depth into tissue, it does not take into account one serious issue—it does not eliminate the direct activation by the one-photon process. This fact explains why, after therapy, patients often need to avoid excessive exposure to sunlight or ambient light for a period of time to reduce photo- toxicity. [10] Avoiding unwanted photochemistry requires a UV-selective filter to block the high-energy light reaching the photoresponsive agent while still retaining the activation by multi-photon processes using longer wavelength light. Herein, we demonstrate an effective way to reduce the access of ultraviolet light to photoresponsive compounds and how they can still be activated by generating the necessary high-energy light using near infrared (NIR) light and upconverting nanoparticles (UCNPs). Our strategy is illus- trated in Scheme 1 and takes advantage of lanthanide-doped NaYF 4 nanoparticles wrapped in a UV-blocking organic polymer. A photochromic dithienylethene derivative is used as a model to demonstrate our concept, which can be applied to photorelease and other phototherapeutic processes. Monodispersed core–shell NaYF 4 nanocrystals containing trivalent Tm 3+ and Yb 3+ ions (NaYF 4 :TmYb) offer an effective way to generate UV and visible light using NIR light. [11–13] These UCNPs absorb several NIR photons (980 nm) and convert them into emissions in the UV and visible regions of the spectrum. We have already shown how these UCNPs can be used to perform photochemistry, release small molecules, and turn on and off fluorescent markers in polymers, in solution and even in live organisms. [14–21] Most of this work was done using photoresponsive dithienylethenes (DTEs), which undergo ring-closing and ring-opening reac- tions between two isomers when exposed to UV and visible light, respectively. [22–24] Because they are relatively well behaved and have different optical properties depending on the isomer, they provide a versatile proof-of-principle model to demonstrate our concept. The two systems (inorganic nanoparticles and organic photoresponsive chromophores) can be combined to generate 1 o-NP (Scheme 1) in which the DTE is anchored to the surface of the UCNPs using “click” chemistry. [15, 19] On the right of Scheme 1 is our hybrid system. The decorated nanoparticles (1 o-NP) are wrapped in a polymer shell composed of polyamide containing PEG chains, one of which is terminated with a known UV-blocking compound. [25] The completely assembled system (1 o-NP-P1) has five distinct layers. The UCNP lies at the core and acts as the NIR-to-UV “light bulb”. It is surrounded by a layer of photoresponsive DTEs, whose role is to report on the success of the concept. The amphiphilic nature of the comb-shaped polymer results in a hydrophobic layer, which stabilizes the assembly, keeps the inner hydrophobic components away from contact with water and ensures the photochemistry of the DTE is maintained, surrounded by a hydrophilic layer as a result of the two PEG chains that project away from the nanoparticle and out into the aqueous environment. The longer of the two PEG chains is terminated with the UV- blocking hydroxy benzophenone, [25] which forms the final UV-light-filtering layer. Because all the layers are transparent to NIR light, this light can still reach the nanoparticle core and be converted into blue and UV light, which will be emitted back out to the photoresponsive layer to trigger the ring-closing reaction. On the other hand, UV light should not penetrate the outer layer. In this way, the multi-photon process can be selectively used and any direct activation of the photochromic DTE by ambient light should be minimized. Details of all synthetic steps are provided in the Support- ing Information. The key step is the assembly of the polymer shell around the DTE-decorated nanoparticles (1 o-NP). Two separate polymers were used to encapsulate these surface modified nanoparticles. The first (P1) contains the UV- blocking compound, the other (P2) does not and is used as a control for our studies. We used the encapsulation method described by Raymo and co-workers [26] and recently used by [*] T. Wu, M. Barker, K.M. Arafeh, J.-C. Boyer, C.-J. Carling, Prof. N. R. Branda Department of Chemistry and 4D LABS Simon Fraser University 8888 University Drive, Burnaby, BC V5A 1S6 (Canada) E-mail: nbranda@sfu.ca [**] This research was supported by the Natural Sciences and Engi- neering Research Council (NSERC) of Canada, the Canada Research Chairs Program and Simon Fraser University. This work made use of 4D LABS shared facilities supported by the Canada Foundation for Innovation (CFI), British Columbia Knowledge Development Fund (BCKDF), and Simon Fraser University. J.-C.B. thanks the Michael Smith Foundation for Health Research (MSFHR) for financial support. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/anie.201305253. A ngewandte Chemi e 1 Angew. Chem. Int. Ed. 2013, 52,1–5  2013 Wiley-VCH Verlag GmbH & Co. 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