Organic triplet-triplet annihilation upconversion (TTA-UC) nanoparticles have emerged as exciting therapeutic agents and imaging probes in recent years due to their unique chemical and optical properties such as outstanding biocompatibility and low power excitation density. In this review, we focus on the latest breakthroughs in such new version of upconversion nanoparticle, including their design, preparation, and applications. First, we will discuss the key principles and design concept of these organic-based photon upconversion in regard to the methods of selection of the related triplet TTA dye pairs (photosensitizer and emitter). Then, we will discuss the recent approaches s to construct TTA-UCNPs including silica TTA-UCNPs, lipid-coated TTA-UCNPs, polymer encapsulated TTA-UCNPs, nano-droplet TTA-UCNPs and metal-organic frameworks (MOFs) constructed TTA-UCNPs. In addition, the applications of TTA-UCNPs will be discussed. Finally, we will discuss the challenges posed by current TTA-UCNP development.

Department of Biochemistry and Molecular Pharmacology University of Massachusetts Medical School Worcester MA 01605 United States

Department of Biochemistry and Molecular Pharmacology University of Massachusetts Medical School Worcester MA 01605 United States; Department of Chemistry and Biochemistry Mendel University in Brno Brno 61300 Czech Republic

Department of Chemistry and Biochemistry Mendel University in Brno Brno 61300 Czech Republic

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Chen G, Qiu H, Prasad PN, Chen X. Upconversion nanoparticles: design, nanochemistry, and applications in theranostics, Chem. Rev 114 (2014) 5161–5214. PubMed PMC

Zhou J, Liu Q, Feng W, Sun Y, Li F. Upconversion luminescent materials: advances and applications, Chem. Rev 115 (2015) 395–465. PubMed

Tu L, Liu X, Wu F, Zhang H. Excitation energy migration dynamics in upconversion nanomaterials, Chem. Soc. Rev 44 (2015) 1331–1345. PubMed

Chen G, Ågren H, Ohulchanskyy TY, Prasad PN. Light upconverting core-shell nanostructures: nanophotonic control for emerging applications, Chem. Soc. Rev 44 (2015) 1680–1713. PubMed

Liu J, Bu W, Pan L, Shi J. NIR-triggered anticancer drug delivery by upconverting nanoparticles with integrated azobenzene-modified mesoporous silica, Angew. Chem 125 (2013) 4471–4475; PubMed

Xing H, Bu W, Zhang S, Zheng X , Li M, Chen F, He Q, Zhou L, Peng W, Hua Y, Shi J. Multifunctional nanoprobes for upconversion fluorescence, MR and CT trimodal imaging, Biomaterials 33 (2012) 1079–1089; PubMed

Liu Y, Meng X, Bu W, Upconversion-based photodynamic cancer therapy. Coordination Chemistry Reviews 379 (2019) 82–98.

Zhou J, Liu Z, Li F. Upconversion nanophosphors for small-animal imaging, Chem. Soc. Rev 41 (2012) 1323–1349. PubMed

Shikha S, Salafi T, Cheng J, Zhang Y. Versatile design and synthesis of nano-barcodes, Chem. Soc. Rev 46 (2017) 7054–7093; PubMed

Yang D, Ma P, Hou Z, Cheng Z, Li C , Lin J. Current advances in lanthanide ion (Ln3+)-based upconversion nanomaterials for drug delivery. Chem. Soc. Rev 44 (2015), 1416–1448; PubMed

Gai S, Li C, Yang P, Lin J. Recent progress in rare earth micro/nanocrystals: soft chemical synthesis, luminescent properties, and biomedical applications. Chem. Rev 114 (2014) 2343–2389. PubMed

Dong H, Du S-R, Zheng X-Y, Lyu G-M, Sun L-D, Li L-D. Lanthanide nanoparticles: From design toward bioimaging and therapy, Chem. Rev 115 (2015) 10725–10815. PubMed

Chen G, Roy I, Yang C, Prasad PN. Nanochemistry and nanomedicine for nanoparticle-based diagnostics and therapy, Chem. Rev 116 (2016) 2826–2885. PubMed

Peng H-Q, Niu L-Y, Chen Y-Z, Wu L-Z, Tung C-H, Yang Q-Z. Biological applications of supramolecular assemblies designed for excitation energy transfer, Chem. Rev 115 (2015) 7502–7542. PubMed

Zhao J, Ji S, Guo H. Triplet–triplet annihilation based upconversion: from triplet sensitizers and triplet acceptors to upconversion quantum yields, RSC Adv 1 (2011) 937–950.

Zhao J, Wu W, Sun J, Guo S. Triplet photosensitizers: from molecular design to applications, Chem. Soc. Rev 42 (2013) 5323–5351. PubMed

Zhao J, Xu K, Yang W, Wang Z, Zhong F. The triplet excited state of Bodipy: formation, modulation and application, Chem. Soc. Rev 44 (2015) 8904–8939. PubMed

Zhu X, Su Q, Feng W, Li F. Anti-Stokes shift luminescent materials for bio-applications, Chem. Soc. Rev 46 (2017) 1025–1039. PubMed

Filatov MA, Baluschevb S, Landfester K. Protection of densely populated excited triplet state ensembles against deactivation by molecular oxygen, Chem. Soc. Rev 45 (2016) 4668–4689. PubMed

Baluschev S, Katta K, Avlasevich Y, Landfester K. Annihilation upconversion in nanoconfinement: solving the oxygen quenching problem, Mater. Horiz 3 (2016) 478–486.

Vadrucci R, Weder C, Simon YC. Organogels for low-power light upconversion, Mater. Horiz 2 (2015) 120–124.

Ji S, Guo H, Wu W, Wu W, Zhao J. Ruthenium (II) polyimine-coumarin dyad with non-emissive 3IL excited state as sensitizer for triplet-triplet annihilation based upconversion, Angew. Chem. Int. Ed 50 (2011) 8283–8286. PubMed

Lu Y, Wang J, McGoldrick N, Cui X, Zhao J, Caverly C, et al., Iridium (III) complexes bearing pyrene-functionalized 1,10-phenanthroline ligands as highly efficient sensitizers for triplet-triplet annihilation upconversion, Angew. Chem. Int. Ed 55 (2016) 14688–14692. PubMed

Borisov SM, Saf R, Fischer R, Klimant I. Synthesis and properties of new phosphorescent red light-excitable platinum (II) and palladium (II) complexes with Schiff bases for oxygen sensing and triplet-triplet annihilation-based upconversion, Inorg. Chem 52 (2013) 1206–1216. PubMed

Yi X, Zhao J, Sun J, Guo S, Zhang H. Visible light-absorbing rhenium(I) tricarbonyl complexes as triplet photosensitizers in photooxidation and triplet-triplet annihilation upconversion, Dalton Trans 42 (2013) 2062–2074. PubMed

Han J, Duan P, Li X, Liu M. Amplification of circularly polarized luminescence through triplet-triplet annihilation-based photon upconversion, J. Am. Chem. Soc 139 (2017) 9783–9786. PubMed

Kim H-l, Kwon OS, Kim S, Choi W, Kim J-H. Harnessing low energy photons (635 nm) for the production of H2O2 using upconversion nanohybrid photocatalysts, Energy Environ. Sci 9 (2016) 1063–1073.

Liu Q, Xu M, Yang T, Tian B, Zhang X, Li F. Highly photostable near-IR-excitation upconversion nanocapsules based on triplet-triplet annihilation for in vivo bioimaging application, ACS Appl. Mater. Interfaces, 10 (2018) 9883–9888. PubMed

Xu K, Zhao J, Escudero D, Mahmood Z, Jacquemin D. Controlling triplet–triplet annihilation upconversion by tuning the PET in aminomethyleneanthracene derivatives, J. Phys. Chem C, 119 (2015) 23801–23812.

Duan P, Yanai N, Nagatomi H, Kimizuka N. Photon upconversion in supramolecular gel matrixes: spontaneous accumulation of light-harvesting donor-acceptor arrays in nanofibers and acquired air stability, J. Am. Chem. Soc 137 (2015) 1887–1894. PubMed

Duan P, Yanai N, Kimizuka N. Photon upconverting liquids: matrix-free molecular upconversion systems functioning in air, J. Am. Chem. Soc 135 (2013) 19056–19059. PubMed

Singh-Rachford TN, Haefele A, Ziessel R, Castellano FN. Boron dipyrromethene chromophores: next generation triplet acceptors/annihilators for low power upconversion schemes, J. Am. Chem. Soc 130 (2008) 16164–16165. PubMed

Wang C, Zhang Q, Wang X, Chang H, Zhang S, Tang Y et al.,. Dynamic modulation of enzyme activity by near-infrared light, Angew. Chem. Int. Ed 56 (2017) 6767–6772. PubMed

Jing T, Dai Y, Wei W, Ma X, Huang B. Near-infrared photocatalytic activity induced by intrinsic defects in Bi2MO6 (M = W, Mo), Phys. Chem. Chem. Phys 16 (2014) 18596–18604. PubMed

Wang Z, Zhao J, Barbon A, Toffoletti A, Liu Y, An Y, et al., Radical-enhanced intersystem crossing in new Bodipy derivatives and application for efficient triplet-triplet annihilation upconversion, J. Am. Chem. Soc 139 (2017) 7831–7842. PubMed

Wu W, Guo H, Wu W, Ji S, Zhao J. Organic triplet sensitizer library derived from a single chromophore (BODIPY) with long-lived triplet excited state for triplet-triplet annihilation based upconversion, J. Org. Chem 76 (2011) 7056–7064. PubMed

Zhang C, Zhao J, Wu S, Wang Z, Wu W, Ma J, et al.,. Intramolecular RET enhanced visible light-absorbing bodipy organic triplet photosensitizers and application in photooxidation and triplet-triplet annihilation upconversion, J. Am. Chem. Soc 135 (2013) 10566–10578. PubMed

Hwang JY, Li Z, Loh XJ. Small molecule therapeutic-loaded liposomes as therapeutic carriers: from development to clinical applications, RSC Adv 6 (2016) 70592–70615.

Grimaldi N, Andrade F, Segovia N, Ferrer-Tasies L, Sala S,Veciana ac J., Ventosa N. Lipid-based nanovesicles for nanomedicine, Chem. Soc. Rev 45 (2016) 6520–6545. PubMed

Chen C, Zhu S, Huang T, Wang S, Yan X. Analytical techniques for single-liposome characterization, Anal. Methods, 5 (2013) 2150–2157.

Askes SHC, Bahreman A, Bonnet S. Activation of a photodissociative ruthenium complex by triplet-triplet annihilation upconversion in liposomes, Angew. Chem. Int. Ed 53 (2014) 1029–1033. PubMed

Gulzar A, Xu J, Yang P, He F, Xu L. Upconversion processes: versatile biological applications and biosafety, Nanoscale, 9 (2017) 12248–12282. PubMed

Wong H-T, Tsang M-K, Chan C-F, Wong K-L, Fei B, Hao J. In vitro cell imaging using multifunctional small sized KGdF4:Yb3+,Er3+ upconverting nanoparticles synthesized by a one-pot solvothermal process, Nanoscale, 5 (2013) 3465–3473. PubMed

Hemmer E, Acosta-Mora P, Méndez-Ramos J, Fischer S. Optical nanoprobes for biomedical applications: shining a light on upconverting and near-infrared emitting nanoparticles for imaging, thermal sensing, and photodynamic therapy, J. Mater. Chem. B, 5 (2017) 4365–4392. PubMed

Mattiello S, Monguzzi A, Pedrini J, Sassi M, Villa C, Torrente Y, et al., Self-assembled dual dye−doped nanosized micelles for high−contrast up−conversion bioimaging, Adv. Funct. Mater 26 (2016) 8447–8454.

Kouno H, Ogawa T, Amemori S, Mahato P, Yanai N, Kimizuka N. Triplet energy migration-based photon upconversion by amphiphilic molecular assemblies in aerated water, Chem. Sci 7 (2016) 5224–5229. PubMed PMC

Poznik M, Faltermeier U, Dick B, König B. Light upconverting soft particles: triplet–triplet annihilation in the phospholipid bilayer of self-assembled vesicles, RSC Adv 6 (2016) 41947–41950.

Yildirim A, Chattaraj R, Blum NT, Goldscheitter GM, Goodwin AP. Stable encapsulation of air in mesoporous silica nanoparticles: fluorocarbon-free nanoscale ultrasound contrast agents, Adv. Healthcare Mater 5 (2016), 1290–1298. PubMed PMC

Niu D, Li Y, Shi J. Silica/organosilica cross-linked block copolymer micelles: a versatile theranostic platform. Chem. Soc. Rev 2017, 46 (2017) 569–585. PubMed

Ma X, Nguyen KT, Borah P, Ang CY, Zhao Y. Functional silica nanoparticles for redox-triggered drug/ssDNA co-delivery, Adv. Healthcare Mater 1 (2012) 690–697. PubMed

Huo Q, Liu J, Wang L-Q, Jiang Y, Lambert TN, Fang E. A new class of silica cross-linked micellar core-shell nanoparticles, J. Am. Chem. Soc 128 (2006) 6447–6453. PubMed

Caltagirone C, Bettoschi A, Garau A, Montis R. Silica-based nanoparticles: a versatile tool for the development of efficient imaging agents, Chem. Soc. Rev 44 (2015) 4645–4671. PubMed

Montalti M, Prodi L, Rampazzo E, Zaccheroni N. Dye-doped silica nanoparticles as luminescent organized systems for nanomedicine, Chem. Soc. Rev 43 (2014) 4243–4268. PubMed

Bonacchi S, Genovese D, Juris R, Montalti M, Prodi L, Rampazzo E, et al.,. Luminescent silica nanoparticles: extending the frontiers of brightness, Angew. Chem. Int. Ed 50 (2011) 4056–4066. PubMed

Liu Q, Yang T, Feng W, Li F. Blue-emissive upconversion nanoparticles for low-power-excited bioimaging in Vivo, J. Am. Chem. Soc 134 (2012) 5390–5397. PubMed

Kwon OS, Kim J-H, Cho JK, Kim J-H. Triplet–triplet annihilation upconversion in CdS-Decorated SiO2 nanocapsules for sub-bandgap photocatalysis, ACS Appl. Mater. Interfaces 7 (2015) 318–325. PubMed

Kwon OS, Song HS, Conde J, Kim H.-l., Artzi N, Kim J-H. Dual-color emissive upconversion nanocapsules for differential cancer bioimaging In Vivo, ACS Nano 10 (2016) 1512–1521. PubMed

Trofymchuk K, Prodi L, Reisch A, Mély Y, Altenhöner K, Mattay J. Exploiting fast exciton diffusion in dye-doped polymer nanoparticles to engineer efficient photoswitching, J. Phys. Chem. Lett 6 (2015) 2259–2264. PubMed

Wu C, Zheng Y, Szymanski C, McNeill J. Energy transfer in a nanoscale multichromophoric system: fluorescent dye-doped conjugated polymer nanoparticles, J. Phys. Chem C, 112 (2008) 1772–1781. PubMed PMC

Li S, Shen X, Li L, Yuan P, Guan Z, Yao SQ, et al.,. Conjugated-polymer-based red-emitting nanoparticles for two-photon excitation cell imaging with high contrast, Langmuir, 30 (2014) 7623–7627. PubMed

Jana B, Bhattacharyya S, Patra A. Functionalized dye encapsulated polymer nanoparticles attached with a BSA scaffold as efficient antenna materials for artificial light harvesting, Nanoscale, 8 (2016), 16034–16043. PubMed

Dryza V, Smith TA, Bieske EJ. Blue to near-IR energy transfer cascade within a dye-doped polymer matrix, mediated by a photochromic molecular switch, Phys. Chem. Chem. Phys 18 (2016) 5095–5098. PubMed

Wu C, Chiu DT. Highly fluorescent semiconducting polymer dots for biology and medicine, Angew. Chem. Int. Ed 52 (2013) 3086–3109. PubMed PMC

Kim J-H, Kim J-H. Triple-emulsion microcapsules for highly efficient multispectral upconversion in the aqueous phase, ACS Photonics, 2 (2015) 633–638.

Wohnhaas C, Friedemann K, Busko D, Landfester K, Baluschev S, Crespy D. All organic nanofibers as ultralight versatile support for triplet–triplet annihilation upconversion, ACS Macro Lett 2 (2013) 446–450. PubMed

Kim J-H, Deng F, Castellano FN, Kim J-H. Red-to-Blue/Cyan/Green upconverting microcapsules for aqueous-and dry-phase color tuning and magnetic sorting, ACS Photonics, 1 (2014) 382–388.

Kang J-H, Lee SS, Guerrero J, Fernandez-Nieves A, Kim S-H, Reichmanis E. Ultrathin double−shell capsules for high performance photon upconversion, Adv. Mater 29 (2017) 1606830. PubMed

Kim J-H, Kim J-H. Encapsulated triplet–triplet annihilation-based upconversion in the aqueous phase for sub-band-gap semiconductor photocatalysis, J. Am. Chem. Soc 134 (2012) 17478–17481. PubMed

Wohnhaas C, Mailänder V, Dröge M, Filatov MA, Busko D, Avlasevich Y. Triplet-triplet annihilation upconversion based nanocapsules for bioimaging under excitation by red and deep-red light, Macromol. Biosci 13 (2013) 1422–1430. PubMed

Askes SHC, Pomp W, Hopkins SL, Kros A, Wu S, Schmidt T, Bonnet S. Imaging upconverting polymersomes in cancer cells: biocompatible antioxidants brighten triplet-triplet annihilation upconversion, Small 12 (2016) 5579–5590. PubMed

Wang W, Liu Q, Zhan C, Barhoumi A, Yang T, Wylie RG et al.,. Efficient triplet–triplet annihilation-based upconversion for nanoparticle phototargeting, Nano Lett 15 (2015) 6332–6338. PubMed

Liu Q, Wang W, Zhan C, Yang T, Kohane DS. Enhanced precision of nanoparticle phototargeting in vivo at a safe irradiance, Nano Lett 16 (2016) 4516–4520. PubMed

Liu Q, Yin B, Yang T, Yang Y, Shen Z, Yao P et al.,. A general strategy for biocompatible, high-effective upconversion nanocapsules based on triplet–triplet annihilation, J. Am. Chem. Soc 135 (2013) 5029–5037. PubMed

Klán P, Šolomek T, Bochet CG, Blanc A, Givens R, Rubina M et al.,. Photoremovable protecting groups in chemistry and biology: reaction mechanisms and efficacy, Chem. Rev 113 (2013), 119–191. PubMed PMC

Kammari L, Šolomek T, Ngoy BP, Heger D, Klán P. Orthogonal photocleavage of a monochromophoric linker, J. Am. Chem. Soc 132 (2010) 11431–11433. PubMed

Lin Q, Bao C, Cheng S, Yang Y, Ji W, Zhu L. Target-activated coumarin phototriggers specifically switch on fluorescence and photocleavage upon bonding to thiol-bearing protein, J. Am. Chem. Soc 134 (2012) 5052–5055. PubMed

Huang L, Zhao Y, Zhang H, Huang K, Yang J, Han G. Expanding anti-stokes shifting in triplet-triplet annihilation upconversion for in vivo anticancer prodrug activation, Angew. Chem. Int. Ed 56 (2017) 14400–14404. PubMed PMC

Chen W, Wu C. Synthesis, functionalization, and applications of metal–organic frameworks in biomedicine. Dalton Trans 47 (2018), 2114–2133; PubMed

Rojas S, Devic T, Horcajada P. Metal organic frameworks based on bioactive components. J. Mater. Chem. B, 5 (2017) 2560–2573. PubMed

Stock N, Biswas S. Synthesis of Metal-Organic Frameworks (MOFs): Routes to Various MOF Topologies, Morphologies, and Composites, Chem. Rev 112 (2012), 933–969. PubMed

Gagnon KJ, Perry HP, Clearfield A. Conventional and unconventional metal–organic frameworks based on phosphonate ligands: MOFs and UMOFs, Chem. Rev 112 (2012), 1034–1054. PubMed

Schoedel A, Li M, Li D, O’Keeffe M, Yaghi OM. Structures of metal–organic frameworks with rod secondary building units, Chem. Rev 116 (2016) 12466–12535. PubMed

Lee CY, Farha OK, Hong BJ, Sarjeant AA, Nguyen ST, Hupp JT. Light-harvesting metal– organic frameworks (MOFs): efficient strut-to-strut energy transfer in Bodipy and porphyrin-based MOFs, J. Am. Chem. Soc 133 (2011) 15858–15861. PubMed

Kent CA, Mehl BP, Ma L, Papanikolas JM, Meyer TJ, Lin W. Energy transfer dynamics in metal−organic frameworks, J. Am. Chem. Soc 132 (2010) 12767–12769. PubMed

Ullman AM, Brown JW, Foster ME, Léonard F, Leong K, Stavila V, Allendorf MD. Transforming MOFs for energy applications using the guest@MOF concept. Inorg. Chem 55 (2016), 7233–7249. PubMed

Zhao X, Song X, Li Y, Chang Z, Chen L. Targeted construction of light-harvesting metal–organic frameworks featuring efficient host–guest energy transfer, ACS Appl. Mater. Interfaces, 10 (2018) 5633–5640. PubMed

Park KC, Seo C, Gupta G, Kim J, Le CY. Efficient energy transfer (EnT) in pyrene−and porphyrin-based mixed-ligand metal–organic frameworks, ACS Appl. Mater. Interfaces, 9 (2017) 38670–38677. PubMed

Park HJ, So MC, Gosztola D, Wiederrecht GP, Emery JD, Martinson ABF et al.,. Layer-by-layer assembled films of perylene diimide−and squaraine-containing metal–organic framework-like materials: Solar energy capture and directional energy transfer, ACS Appl. Mater. Interfaces, 8 (2016) 24983–24988. PubMed

Park J, Xu M, Li F, Zhou H-C. 3D long-range triplet migration in a water-stable metal–organic framework for upconversion-based ultralow-power in vivo imaging, J. Am. Chem. Soc 140 (2018) 5493–5499. PubMed

Hosoyamada M, Yanai N, Okumura K, Uchihashi T, Kimizuka N. Translating MOF chemistry into supramolecular chemistry: soluble coordination nanofibers showing efficient photon upconversion, Chem. Commun 54 (2018) 6828–6831. PubMed