Blue-emissive upconversion nanoparticles for low-power-excited bioimaging in vivo

Water-soluble upconversion luminescent (UCL) nanoparticles based on triplet-triplet annihilation (TTA) were successfully prepared by coloading sensitizer (octaethylporphyrin Pd complex) and annihilator (9,10-diphenylanthracene) into silica nanoparticles. The upconversion luminescence quantum yield of the nanoparticles can be as high as 4.5% in aqueous solution. As determined by continuous kinetic scan, the nanoparticles have excellent photostability. Such TTA-based upconversion nanoparticles show low cytotoxicity and were successfully used to label living cells with very high signal-to-noise ratio. UCL imaging with the nanoparticles as probe is capable of completely eliminating background fluorescence from either endogenous fluorophores of biological sample or the colabeled fluorescent probe. In particular, such blue-emissive upconversion nanoparticles were successfully applied in lymph node imaging in vivo of living mouse with excellent signal-to-noise ratio (>25), upon low-power density excitation of continuous-wave 532 laser (8.5 mW cm(-2)). Such high-contrast and low-power excited bioimaging in vivo with a blue-emissive upconversion nanoparticle as probe may extend the arsenal of currently available luminescent bioimaging in vitro and in vivo.     

Pd–Porphyrin Oligomers Sensitized for Green‐to‐Blue Photon Upconversion: The More the Better?

A series of directly meso‐meso‐linked Pd–porphyrin oligomers (PdDTP‐M, PdDTP‐D, and PdDTP‐T) have been prepared. The absorption region and the light‐harvesting ability of the Pd–porphyrin oligomers are broadened and enhanced by increasing the number of Pd–porphyrin units. Triplet–triplet annihilation upconversion (TTA‐UC) systems were constructed by utilizing the Pd–porphyrin oligomers as the sensitizer and 9,10‐diphenylanthracene (DPA) as the acceptor in deaerated toluene and green‐to‐blue photon upconversion was observed upon excitation with a 532 nm laser. The triplet–triplet annihilation upconversion quantum efficiencies were found to be 6.2 %, 10.5 %, and 1.6 % for the [PdDTP‐M]/DPA, [PdDTP‐D]/DPA, and [PdDTP‐T]/DPA systems, respectively, under an excitation power density of 500 mW cm^?2. The photophysical processes of the TTA‐UC systems have been investigated in detail. The higher triplet–triplet annihilation upconversion quantum efficiency observed in the [PdDTP‐D]/DPA system can be rationalized by the enhanced light‐harvesting ability of PdDTP‐D at 532 nm. Under the same experimental conditions, the [PdDTP‐D]/DPA system produces more ³DPA* than the other two TTA‐UC systems, benefiting the triplet–triplet annihilation process. This work provides a useful way to develop efficient TTA‐UC systems with broad spectral response by using Pd–porphyrin oligomers as sensitizers.     

Lanthanide‐Doped LiLuF4 Upconversion Nanoprobes for the Detection of Disease Biomarkers

Lanthanide‐doped upconversion nanoparticles (UCNPs) have shown great promise in bioapplications. Exploring new host materials to realize efficient upconversion luminescence (UCL) output is a goal of general concern. Herein, we develop a unique strategy for the synthesis of novel LiLuF₄:Ln³⁺ core/shell UCNPs with typically high absolute upconversion quantum yields of 5.0 % and 7.6 % for Er³⁺ and Tm³⁺, respectively. Based on our customized UCL biodetection system, we demonstrate for the first time the application of LiLuF₄:Ln³⁺ core/shell UCNPs as sensitive UCL bioprobes for the detection of an important disease marker β subunit of human chorionic gonadotropin (β‐hCG) with a detection limit of 3.8 ng mL⁻¹, which is comparable to the β‐hCG level in the serum of normal humans. Furthermore, we use these UCNPs in proof‐of‐concept computed tomography imaging and UCL imaging of cancer cells, thus revealing the great potential of LiLuF₄:Ln³⁺ UCNPs as efficient nano‐bioprobes in disease diagnosis.     

Tuning the emissive triplet excited states of platinum(II) Schiff base complexes with pyrene, and application for luminescent oxygen sensing and triplet-triplet-annihilation based upconversions

Pt(II) Schiff base complexes containing pyrene subunits were prepared using the chemistry-on-complex approach. This is the first time that supramolecular photochemical approach has been used to tune the photophysical properties of Schiff base Pt(II) complexes, such as emission wavelength and lifetimes. The complexes show intense absorption in the visible region (ε = 13100 M(-1) cm(-1) at 534 nm) and red phosphorescence at room temperature. Notably, much longer triplet excited state lifetimes (τ = 21.0 μs) were observed, compared to the model complexes (τ = 4.4 μs). The extension of triplet excited state lifetimes is attributed to the establishment of equilibrium between the metal-to-ligand charge-transfer ((3)MLCT) state (coordination centre localized) and the intraligand ((3)IL) state (pyrene localized), or population of the long-lived (3)IL triplet excited state. These assignments were fully rationalized by nanosecond time-resolved difference absorption spectra, 77 K emission spectra and density functional theory calculations. The complexes were used as triplet sensitizers for triplet-triplet-energy-tranfer (TTET) processes, i.e. luminescent O(2) sensing and triplet-triplet annihilation (TTA) based upconversion. The O(2) sensitivity (Stern-Volmer quenching constant) of the complexes was quantitatively evaluated in polymer films. The results show that the O(2) sensing sensitivity of the pyrene containing complex (K(SV) = 0.04623 Torr(-1)) is 15-fold of the model complex (K(SV) = 0.00313 Torr(-1)). Furthermore, significant TTA upconversion (upconversion quantum yield Φ(UC) = 17.7% and the anti-Stokes shift is 0.77 eV) was observed with pyrene containing complexes being used as triplet sensitizers. Our approach to tune the triplet excited states of Pt(II) Schiff base complexes will be useful for the design of phosphorescent transition metal complexes and their applications in light-harvesting, photovoltaics, luminescent O(2) sensing and upconversion, etc.     

New Anthracene Derivatives as Triplet Acceptors for Efficient Green‐to‐Blue Low‐Power Upconversion

Three new anthracene derivatives [2‐chloro‐9,10‐dip‐tolylanthracene (DTACl), 9,10‐dip‐tolylanthracene‐2‐carbonitrile (DTACN), and 9,10‐di(naphthalen‐1‐yl)anthracene‐2‐carbonitrile (DNACN)] were synthesized as triplet acceptors for low‐power upconversion. Their linear absorption, single‐photon‐excited fluorescence, and upconversion fluorescence properties were studied. The acceptors exhibit high fluorescence yields in DMF. Selective excitation of the sensitizer Pd^IIoctaethylporphyrin (PdOEP) in solution containing DTACl, DTACN, or DNA‐CN at 532 nm with an ultralow excitation power density of 0.5 W cm^?2 results in anti‐Stokes blue emission. The maximum upconversion quantum yield (Φ_UC=17.4 %) was obtained for the couple PdOEP/DTACl. In addition, the efficiency of the triplet–triplet energy transfer process was quantitatively studied by quenching experiments. Experimental results revealed that a highly effective acceptor for upconversion should combine high fluorescence quantum yields with efficient quenching of the sensitizer triplet.     

Enhancing Dye-Triplet-Sensitized Upconversion Emission Through the Heavy-Atom Effect in CsLu2F7:Yb/Er Nanoprobes

Lanthanide (Ln³⁺)-doped upconversion (UC) nanoprobes, which have drawn extensive attention for various bioapplications, usually suffer from small absorption cross-sections and weak luminescence intensity of Ln³⁺ ions. Herein, we report the controlled synthesis of a new class of Ln³⁺-doped UC nanoprobes based on CsLu₂F₇:Yb/Er nanocrystals (NCs), which can effectively increase the intersystem crossing (ISC) efficiency from singlet excited state to triplet excited state of IR808 up to 99.3 % through the heavy atom effect. By virtue of the efficient triplet sensitization of IR808, the optimal UC luminescence (UCL) intensity of IR808-modified CsLu₂F₇:Yb/Er NCs is enhanced by 1309 times upon excitation at 808 nm. Benefiting from the intense dye-triplet-sensitized UCL, the nanoprobes are demonstrated for sensitive assay of extracellular and intracellular hypochlorite with an 808-nm/980-nm dual excited ratiometric strategy.     

A TDDFT investigation of bay substituted perylenediimides: Absorption and intersystem crossing

The conformational structure and electronic spectra properties of a series of bay substituted perylenediimides (PDI) derivatives have been investigated by means of density functional theory (DFT) and time‐dependent DFT. The B3LYP and PBE0 hybrid exchange‐correlation functionals were applied in conjunction with the double‐ζ quality SVP basis set. These compounds are interesting for organic materials science and as photosensitizers in cancer phototherapy (PDT), because of their intense absorption in the visible region. Results show that the substitution at the bay position of the PDI parent molecule with N‐alkyl groups shifts the absorption maxima towards the red part of the visible spectrum (around 650–700 nm) as required for the applications in PDT. The main PDT action mechanisms have been investigated by computing of electron affinities, ionization potentials, triplet energies and spin‐orbit matrix elements between singlet and triplet excited states. © 2012 Wiley Periodicals, Inc.     

Characterization of photoinduced isomerization and intersystem crossing of the cyanine dye Cy3

Several important photophysical properties of the cyanine dye Cy3 have been determined by laser flash photolysis. The triplet-state absorption and photoisomerization of Cy3 are distinguished by using the heavy-atom effects and oxygen-induced triplet --> triplet energy transfer. Furthermore, the triplet-state extinction coefficient and quantum yield of Cy3 are also measured via triplet-triplet energy-transfer method and comparative actinometry, respectively. It is found that the triplet --> triplet (T1-->Tn) absorptions of trans-Cy3 largely overlap the ground-state absorption of cis-Cy3. Unlike what occurred in Cy5, we have not observed the triplet-state T1-->Tn absorption of cis-Cy3 and the phosphorescence from triplet state of cis-Cy3 following a singlet excitation (S0-S1) of trans-Cy3, indicating the absence of a lowest cis-triplet state as an isomerization intermediate upon excitation in Cy3. The detailed spectra of Cy3 reported in this paper could help us interpret the complicated photophysics of cyanine dyes.     

Nd3+‐Sensitized Upconversion Metal–Organic Frameworks for Mitochondria‐Targeted Amplified Photodynamic Therapy

Herein, we report the design and synthesis of a mitochondria‐specific, 808 nm NIR light‐activated photodynamic therapy (PDT) system based on the combination of metal–organic frameworks (MOFs) and upconversion photochemistry with an organelle‐targeting strategy. The system was synthesized through the growth of a porphyrinic MOF on Nd³⁺‐sensitized upconversion nanoparticles to achieve Janus nanostructures with further asymmetric functionalization of the surface of the MOF domain. The PDT nanoplatform allows for photosensitizing with 808 nm NIR light, which could effectively avoid the laser‐irradiation‐induced overheating effect. Furthermore, mitochondria‐targeting could amplify PDT efficacy through the depolarization of the mitochondrial membrane and the initiation of intrinsic apoptotic pathway. This work sheds light on the hybrid engineering of MOFs to combat their current limitations for PDT.     

Stimuli‐Responsive Dual‐Color Photon Upconversion: A Singlet‐to‐Triplet Absorption Sensitizer in a Soft Luminescent Cyclophane

Reversible emission color switching of triplet–triplet annihilation‐based photon upconversion (TTA‐UC) is achieved by employing an Os complex sensitizer with singlet‐to‐triplet (S‐T) absorption and an asymmetric luminescent cyclophane with switchable emission characteristics. The cyclophane contains the 9,10‐bis(phenylethynyl)anthracene unit as an emitter and can assemble into two different structures, a stable crystalline phase and a metastable supercooled nematic phase. The two structures exhibit green and yellow fluorescence, respectively, and can be accessed by distinct heating/cooling sequences. The hybridization of the cyclophane with the Os complex allows near‐infrared‐to‐visible TTA‐UC. The large anti‐Stokes shift is possible by the direct S‐T excitation, which dispenses with the use of a conventional sequence of singlet–singlet absorption and intersystem crossing. The TTA‐UC emission color is successfully switched between green and yellow by thermal stimulation.     

球形Y2O2S∶Yb,Ho上转换粒子的合成及其尺寸相关的发光机制研究

采用改进的均匀沉淀法结合固-气硫化工艺制备了一系列Y2O2S∶Yb, Ho上转换粒子. 利用X射线晶体衍射(XRD)和透射电子显微镜(TEM)对粒子的结构和形貌进行了表征, 并通过上转换发光光谱(UCL)和红外光谱(FTIR)研究了粒子的上转换发光性质. XRD和TEM结果表明, 所制备的样品均为单一的六方相结构, 且所有粒子均呈单分散和尺寸均一的球形, 其尺寸分别为40, 80和200 nm. 根据发光强度和激发功率间的对数关系曲线发现, 随着粒子尺寸的降低, 蓝光发射由三光子吸收过程转变为双光子吸收过程; 而绿光和红光发射虽然一直保持双光子吸收过程, 但其对数曲线斜率均随粒子尺寸的降低而逐渐增大. 对该材料的粒子尺寸与上转换发光机制的关系进行了讨论.     

Filtration Shell Mediated Power Density Independent Orthogonal Excitations–Emissions Upconversion Luminescence

Lanthanide doped core–multishell structured NaGdF₄:Yb,Er@NaYF₄:Yb@NaGdF₄:Yb,Nd@NaYF₄@NaGdF₄:Yb,Tm@NaYF₄ nanoparticles with power‐density independent orthogonal excitations‐emissions upconversion luminescence (UCL) were fabricated for the first time. The optical properties of these core–multishell structured nanoparticles were related to the absorption filtration effect of the NaGdF₄:Yb,Tm layer. By tuning the thickness of the filtration layer, the nanoparticles can exhibit unique two independent groups of UCL: Tm³⁺ prominent UV/blue (UV=ultraviolet) UCL under the excitation at 980 nm and Er³⁺ prominent green/red UCL under the excitation at 796 nm. The filtration‐shell mediated orthogonal excitations‐emissions UCL are power‐density independent. As a proof of concept, the core–multishell nanoparticles are used in multi‐dimensional security design and imaging‐guided combined photodynamic therapy and chemotherapy.     

Long-Lived Triplet Excited State Accessed with Spin–Orbit Charge Transfer Intersystem Crossing in Red Light-Absorbing Phenoxazine-Styryl BODIPY Electron Donor/Acceptor Dyads

Orthogonal phenoxazine-styryl BODIPY compact electron donor/acceptor dyads were prepared as heavy atom-free triplet photosensitizers (PSs) with strong red light absorption (ϵ=1.33×10⁵ M⁻¹ cm⁻¹ at 630 nm), whereas the previously reported triplet photosensitizers based on the spin-orbit charge transfer intersystem crossing (SOCT-ISC) mechanism show absorption in a shorter wavelength range (<500 nm). More importantly, a long-lived triplet state (τ_T=333 μs) was observed for the new dyads. In comparison, the triplet state lifetime of the same chromophore accessed with the conventional heavy atom effect (HAE) is much shorter (τ_T=1.8 μs). Long triplet state lifetime is beneficial to enhance electron or energy transfer, the primary photophysical processes in the application of triplet PSs. Our approach is based on SOCT-ISC, without invoking of the HAE, which may shorten the triplet state lifetime. We used bisstyrylBodipy both as the electron acceptor and the visible light-harvesting chromophore, which shows red-light absorption. Femtosecond transient absorption spectra indicated the charge separation (109 ps) and SOCT-ISC (charge recombination, CR; 2.3 ns) for BDP-1 . ISC efficiency of BDP-1 was determined as Φ_T=25 % (in toluene). The dyad BDP-3 was used as triplet PS for triplet-triplet annihilation upconversion (upconversion quantum yield Φ_UC=1.5 %; anti-Stokes shift is 5900 cm⁻¹).     

Heavy atom-free triplet photosensitizer based on thermally activated delayed fluorescence material for NIR-to-blue triplet-triplet annihilation upconversion

Triplet-triplet annihilation (TTA) upconversion-based materials have potential application in the broad range of research areas, including photocatalysis and life sciences. However, near-infrared (NIR)-to-blue upconverted emission is preferred for most of the practical applications, but developing a NIR-to-blue TTA upconversion system is a challenging task in photochemistry. In this work, a thermally activated delayed fluorescence (TADF) material with intense visible-to-NIR absorption is demonstrated that shows a longer triplet state lifetime (32 µs) and high triplet state energy (E_T = 1.55 eV). For the first time, a heavy atom-free NIR (λ_ex > 650 nm) to blue (λ_em< 460 nm) TTA upconversion system was devised, employing the dimeric borondifluoride curcuminoid TADF material as triplet photosensitizer (PS) and a large anti-Stokes shift (0.88 eV) along with moderate upconversion yield was achieved. Our work provides the solution and guidance for the future development of purely organic heavy atom-free NIR activating TTA upconversion system for a wide array of applications.     

Spin–Orbit Charge-Transfer Intersystem Crossing (ISC) in Compact Electron Donor–Acceptor Dyads: ISC Mechanism and Application as Novel and Potent Photodynamic Therapy Reagents

Spin–orbit charge-transfer intersystem crossing (SOCT-ISC) is useful for the preparation of heavy atom-free triplet photosensitisers (PSs). Herein, a series of perylene-Bodipy compact electron donor/acceptor dyads showing efficient SOCT-ISC is prepared. The photophysical properties of the dyads were studied with steady-state and time-resolved spectroscopies. Efficient triplet state formation (quantum yield Φ_T=60 %) was observed, with a triplet state lifetime (τ_T=436 μs) much longer than that accessed with the conventional heavy atom effect (τ_T=62 μs). The SOCT-ISC mechanism was unambiguously confirmed by direct excitation of the charge transfer (CT) absorption band by using nanosecond transient absorption spectroscopy and time-resolved electron paramagnetic resonance (TREPR) spectroscopy. The factors affecting the SOCT-ISC efficiency include the geometry, the potential energy surface of the torsion, the spin density for the atoms of the linker, solvent polarity, and the energy matching of the ¹CT/³LE states. Remarkably, these heavy atom-free triplet PSs were demonstrated as a new type of efficient photodynamic therapy (PDT) reagents (phototoxicity, EC₅₀=75 nm ), with a negligible dark toxicity (EC₅₀=78.1 μm ) compared with the conventional heavy atom PSs (dark toxicity, EC₅₀=6.0 μm, light toxicity, EC₅₀=4.0 nm ). This study provides in-depth understanding of the SOCT-ISC, unveils the design principles of triplet PSs based on SOCT-ISC, and underlines their application as a new generation of potent PDT reagents.     

Elucidation of the Intersystem Crossing Mechanism in a Helical BODIPY for Low‐Dose Photodynamic Therapy

Intersystem crossing (ISC) of triplet photosensitizers is a vital process for fundamental photochemistry and photodynamic therapy (PDT). Herein, we report the co‐existence of efficient ISC and long triplet excited lifetime in a heavy atom‐free bodipy helicene molecule. Via theoretical computation and time‐resolved EPR spectroscopy, we confirmed that the ISC of the bodipy results from its twisted molecular structure and reduced symmetry. The twisted bodipy shows intense long wavelength absorption (?=1.76×10⁵ m ^?1 cm^?1 at 630 nm), satisfactory triplet quantum yield (Φ_T=52 %), and long‐lived triplet state (τ_T=492 μs), leading to unprecedented performance as a triplet photosensitizer for PDT. Moreover, nanoparticles constructed with such helical bodipy show efficient PDT‐mediated antitumor immunity amplification with an ultra‐low dose (0.25 μg kg^?1), which is several hundred times lower than that of the existing PDT reagents.     

Elucidation of the Intersystem Crossing Mechanism in a Helical BODIPY for Low-Dose Photodynamic Therapy

Intersystem crossing (ISC) of triplet photosensitizers is a vital process for fundamental photochemistry and photodynamic therapy (PDT). Herein, we report the co-existence of efficient ISC and long triplet excited lifetime in a heavy atom-free bodipy helicene molecule. Via theoretical computation and time-resolved EPR spectroscopy, we confirmed that the ISC of the bodipy results from its twisted molecular structure and reduced symmetry. The twisted bodipy shows intense long wavelength absorption (ϵ=1.76×10⁵ m ⁻¹ cm⁻¹ at 630 nm), satisfactory triplet quantum yield (Φ_T=52 %), and long-lived triplet state (τ_T=492 μs), leading to unprecedented performance as a triplet photosensitizer for PDT. Moreover, nanoparticles constructed with such helical bodipy show efficient PDT-mediated antitumor immunity amplification with an ultra-low dose (0.25 μg kg⁻¹), which is several hundred times lower than that of the existing PDT reagents.     

局域结构依赖的稀土上转换发光

稀土掺杂上转换发光纳米材料作为一种新型的荧光材料,因其发光性能优异、化学性质稳定以及自发荧光干扰小等优点受到国内外研究者的广泛关注.如何实现稀土上转换发光性能的可控调节一直是稀土纳米发光材料研究中的一个热点问题.简要总结了近年来关于局域结构依赖的稀土上转换发光性能的研究进展,分别从结构设计和晶体结构调节两个方面展开,主...     

Enhanced red emission from GdF3:Yb3+,Er3+ upconversion nanocrystals by Li+ doping and their application for bioimaging

Under 980?nm near-infrared (NIR) excitation, upconversion luminescent (UCL) emission of GdF(3):Yb,Er upconversion nanoparticles (UCNPs) synthesized by a simple and green hydrothermal process can be tuned from yellow to red by varying the concentration of dopant Li(+) ions. A possible mechanism for enhanced red upconverted radiation is proposed. A layer of silica was coated onto the surface of GdF(3):Yb,Er,Li UCNPs to improve their biocompatibility. The silica-coated GdF(3):Yb,Er,Li UCNPs show great advantages in cell labeling and in vivo optical imaging. Moreover, GdF(3) UCNPs also exhibited a positive contrast effect in T(1)-weighted magnetic resonance imaging (MRI). These results suggest that the GdF(3) UCNPs could act as dual-modality biolabels for optical imaging and MRI.     

Aqueous-phase synthesis of upconversion metal-organic frameworks for ATP-responsive in situ imaging and targeted combinational cancer therapy

Herein, the nanoscaled ATP-responsive upconversion metal-organic frameworks（UCMOFs） are aqueousphase synthesized for co-delivery of therapeutic protein cytochrome c（Cyt c） and chemodrugs doxorubicin（DOX）, achieving targeted combinational therapy of human cervical cancer. The UCMOFs are rationally fabricated by growing ZIF-90 on mesoporous silica-coated upconversion nanoparticles（UCNPs）,in which the ZIF-90 layer attenuates the upconversion luminescence（UCL） and the rigid frameworks increase the s...