Enhancing NIR-II Upconversion Monochromatic Emission for Temperature Sensing.

The upconversion luminescence (UCL) in the second near-infrared window (NIR-II) is highly attractive due to its excellent performance in high-resolution bioimaging, anticounterfeiting, and temperature sensing. However, upconvertion nanoparticles (UCNPs) are normally emitted in visible light, potentially impacting the imaging quality. Here, a monochromatic Er3+-rich (NaErF4:x%Yb@NaYF4) nanoparticles with excitation at 1532 nm and emission at 978 nm is proposed, both situated in the NIR-II region. The proper proportion of Yb3+ ions doping has a positive effect on the NIR-II emission, by enhancing the cross relaxation efficiency and accelerating the energy transfer rate. Owing to the interaction between the Er3+ and Yb3+ is inhibited at low temperatures, the UCL emission intensities at visible and NIR-II regions show opposite trend with temperature changing, which establishes a fitting formula to derive temperature from the luminous intensity ratio, promoting the potential application of UCL in NIR-II regions for the temperature sensing.

Manipulating the Injected Energy Flux via Host-Sensitized Nanostructure for Improving Multiphoton Upconversion Luminescence of Tm3.

Combating the concentration quenching effect by increasing the concentration of sensitized rare-earth ions in rational design upconversion nanostructure will make it easier to utilize injection energy flux and transfer it to emitters, resulting in improved upconversion luminescence (UCL). We proposed a host-sensitized nanostructure (active core@luminescent shell@inert shell) to improve multiphoton UCL of Tm3+ based on the LiLnF4 host. Yb3+ ions were isolated in the core as energy absorbents, and Tm3+ was doped in the interior LiYbF4 host shell. Compared with sandwich structured nanocrystals (Y@Y:Yb/Tm@Y), reverse structure (YbTm@Yb@Y), and fully doped structure (YbTm@YbTm@Y), the proposed structure achieved the highest efficiency of multiphoton UCL and favored a better FRET-based application performance as the Tm3+ located at an optimized spatial distribution. Furthermore, steady-state and dynamic analysis results demonstrate that by manipulating the spatial distribution of the active ions, excited energy can be tuned to enable multiphoton upconversion enhancement, overcoming the conventional limitations.

Significant Enhancement of the Upconversion Emission in Highly Er3+ -Doped Nanoparticles at Cryogenic Temperatures.

Relatively low efficiency is the bottleneck for the application of lanthanide-doped upconversion nanoparticles (UCNPs). The high-level doping strategy realized in recent years has not improved the efficiency as much as expected. It is argued that cross relaxation (CR) is not detrimental to upconversion. Here we combine theoretical simulation and spectroscopy to elucidate the role of CR in upconversion process of Er3+ highly doped (HD) UCNPs. It is found that if CR is purposively suppressed, upconversion efficiency can be significantly improved. Specifically, we demonstrate experimentally that inhibition of CR by introducing cryogenic environment (40 K) enhances upconversion emission by more than two orders of magnitude. This work not only elucidates the nature of CR and its non-negligible adverse effects, but also provides a new perspective for improving upconversion efficiency. The result can be directly applied to cryogenic imaging and wide range temperature sensing.

Cross Relaxation Channel Tailored Temperature Response in Er3+ -rich Upconversion Nanophosphor.

Recently high doping of lanthanide ions (till 100 %) is realized unprecedentedly in nanostructured upconversion (UC) phosphors. However, oddly enough, this significant breakthrough did not result in a corresponding UC enhancement at ambient temperature, which hinders the otherwise very interesting applications of these materials in various fields. In this work, taking the Er3+ -rich UC nanosystem as an example, we confirm unambiguously that the phonon-assisted cross relaxation (CR) is the culprit. More importantly, combining the theoretical modeling and experiments, the precise roles of different CR channels on UC energy loss are quantitatively revealed. As a result, lowering the temperature can exponentially enhance the relevant UC luminescence by more than two orders of magnitude. Our comprehension will play an important role in promoting the UC performance and further application of high doping rare earth materials. As a proof of concept, an Er3+ -rich core/multi-shell nanophosphor is exploited which demonstrates the great potential of our finding in the field of ultra-sensitive temperature sensing.

Precisely Tailoring Upconversion Dynamics via Energy Migration in Core-Shell Nanostructures.

Upconversion emission dynamics have long been believed to be determined by the activator and its interaction with neighboring sensitizers. Herein this assumption is, however, shown to be invalid for nanostructures. We demonstrate that excitation energy migration greatly affects upconversion emission dynamics. "Dopant ions' spatial separation" nanostructures are designed as model systems and the intimate link between the random nature of energy migration and upconversion emission time behavior is unraveled by theoretical modelling and confirmed spectroscopically. Based on this new fundamental insight, we have successfully realized fine control of upconversion emission time behavior (either rise or decay process) by tuning the energy migration paths in various specifically designed nanostructures. This result is significant for applications of this type of materials in super resolution spectroscopy, high-density data storage, anti-counterfeiting, and biological imaging.

Excitation energy migration dynamics in upconversion nanomaterials.

Recent efforts and progress in unraveling the fundamental mechanism of excitation energy migration dynamics in upconversion nanomaterials are covered in this review, including short- and long-term interactions and other interactions in homogeneous and heterogeneous nanostructures. Comprehension of the role of spatial confinement in excitation energy migration processes is updated. Problems and challenges are also addressed.

Controlling the fluorescent properties of aqueous CdTe nanocrystals by modulating the growth rate.

Although high quality aqueous CdTe and CdTeS alloyed quantum dots (QDs) have been synthesized in recent years, the relationship between the fluorescent properties and the growth kinetics has not been well documented yet. In this paper, 3-mercaptopropionic acid stabilized aqueous CdTe nanocrystals (NCs) are generally prepared with an improvement of the "traditional" synthetic approach, where the preparation of the red emission NCs is usually time-consuming due to the slow growth rate. The investigation on the kinetic and thermodynamic growth process shows that the growth can be effectively accelerated by decreasing the ligand concentration from 0.06 to 0.01 mol/L or elevating the growth temperature from 120 to 240 degrees C. In contrast to previous results, the quantum yield (QY) of the CdTe NCs is heightened to 45% only by increasing properly the growth rate. Our experiments depict that high growth rate favours high concentration of free monomers and thus decreases the number of the surface Te atoms of the NCs, leading to the enhancement of the photoluminescence (PL) QY.

A scintillating nanoplatform with upconversion function for the synergy of radiation and photodynamic therapies for deep tumors.

Collaborative therapy is regarded as an effective approach in increasing the therapeutic efficacy of cancer. In this work, we have proposed and validated the concept of upconversion lumienscence image guided synergy of photodynamic therapy (PDT) and radiotherapy (RT) for deep cancer, via a specially designed nanoplatform integrating near infrared (NIR) light activated luminescence upconversion and X-ray induced scintillation. Upon NIR light irradiation, the nanoplatform emits highly monochromatic red light solely for imaging the targeted cancer cells without triggering therapy; however, when the irradiation turns to a low dose of X-rays, scintillation will occur which induces effectively the PDT destroying the cancer cells together with X-ray induced RT. The novel theranostic nanoplatform is constructed in such a way that the interactions between the upconversion core and the outmost scintillating shell are blocked effectively by an inert layer between them. This structural design not only enables a nearly perfect excitation energy delivery (∼100% at a spectral overlapping wavelength of ∼540 nm) from the outermost scintellating layer to the surface-anchored photosensitizers and so a maximum yield of radical oxygen species, but also achieves a strong NIR induced upconversion luminescence for imaging. Since PDT and RT attack different parts of a cancer cell, this synergy is more effective in destroying cancer than a single therapy, resulting in the reduction of the X-ray irradiation dosage. As a proof of principle, the theranostic effect is validated by in vitro and in vivo experiments, exhibiting the great potential of this sort of nanoplatform in deep cancer treatment.

Internal OH- induced cascade quenching of upconversion luminescence in NaYF4:Yb/Er nanocrystals.

Internal hydroxyl impurity is known as one of the main detrimental factors affecting the upconversion (UC) efficiency of upconversion luminescence (UCL) nanomaterials. Different from surface/ligand-related emission quenching which can be effectively diminished by, e.g., core/shell structure, internal hydroxyl is easy to be introduced in synthesis but difficult to be quantified and controlled. Therefore, it becomes an obstacle to fully understand the relevant UC mechanism and improve UC efficiency of nanomaterials. Here we report a progress in quantifying and large-range adjustment of the internal hydroxyl impurity in NaYF4 nanocrystals. By combining the spectroscopy study and model simulation, we have quantitatively unraveled the microscopic interactions underlying UCL quenching between internal hydroxyl and the sensitizers and activators, respectively. Furthermore, the internal hydroxyl-involved UC dynamical process is interpreted with a vivid concept of "Survivor effect," i.e., the shorter the migration path of an excited state, the larger the possibility of its surviving from hydroxyl-induced quenching. Apart from the consistent experimental results, this concept can be further evidenced by Monte Carlo simulation, which monitors the variation of energy migration step distribution before and after the hydroxyl introduction. The new quantitative insights shall promote the construction of highly efficient UC materials.

Hybrid Nanoplatform: Enabling a Precise Antitumor Strategy via Dual-Modal Imaging-Guided Photodynamic/Chemo-/Immunosynergistic Therapy.

Photodynamic therapy (PDT) has been widely used in tumor therapy due to its high spatial-temporal control and noninvasiveness. However, its clinical application is limited by weak efficacy, shallow tissue penetration, and phototoxicity. Herein, a facile theranostic nanoplatform based on photoswitchable lanthanide-doped nanoparticles was designed. Typically, these nanoparticles had UV-blue and 1525 nm emission upon 980 nm excitation and 1525 nm emission upon 800 nm excitation. We further used these nanoparticles for achieving real-time near-infrared (NIR)-IIb imaging (800 nm) with a high signal-to-noise ratio and imaging-guided PDT (980 nm). Moreover, such a photoswitchable nanoplatform capping with pH-sensitive calcium phosphate for coloading doxorubicin (a chemotherapeutic immunogenic cell death [ICD] inducer) and paramagnetic Mn2+ ions enhances T1-magnetic resonance imaging in the tumor microenvironment. Our results suggest that this theranostic nanoplatform could not only kill tumor cells directly through dual-modal image-guided PDT/chemotherapy but also inhibit distant tumor and lung metastasis through ICD. Therefore, it has great potential for clinical application .

Spectroscopic study of the authentic emitter of AMPPD chemiluminescence in alkaline aqueous solution.

To design more effective CIEEL (chemically initiated electron exchange luminescence) systems demands a complete picture of the dynamics of the chemiluminescence, which is often a challenge. In this work, photoluminescence of the methyl m-oxybenzoate anion - the authentic emitter of AMPPD (3-[2-spiroadamantane]-4-methoxy-4-[3-phosphoryloxy]-phenyl-1,2-dioxetane) in aqueous solvent has been studied. Combining the effect of solvent properties, e.g. pH value, and spectroscopic studies employing steady-state and ultrafast time-resolved emission and absorption and (1)H NMR techniques, a novel mechanism is proposed. We conclude that the deviation of emission peaks between chemiluminescence and photoluminescence of the authentic emitter of AMPPD i.e. the methyl m-oxybenzoate anion, in alkaline aqueous solvents is due to its hydrolysis, rather than the hydrogen-bonding effect as has been assumed so far. Besides, the hydrogen-bonding is suggested to play a key role in significantly decreasing the chemiluminescence yield of AMPPD in aqueous solution by shortening the lifetime of the excited authentic emitter to 10 ps order of magnitude - three orders of magnitude shorter than the previously reported value ( approximately 10 ns). These results shed light on the chemiluminescence dynamics of AMPPD and facilitate the design of more effective CIEEL systems.

Assembly of upconversion nanophotosensitizer in vivo to achieve scatheless real-time imaging and selective photodynamic therapy.

A perfect "off" to "on" switch of the therapeutic function is very important to minimize the phototoxicity of nanoplatforms assisted imaging-guided photodynamic therapy (PDT) of cancer. Current approaches rely on preloaded photosensitizers, where the off/on state of PDT is regulated by the sensitizing light of photosensitizers. However, the photoactivities inevitably occur when imaging/diagnosis or exposure to sunlight, etc. These preloading approaches will cause the damage to normal cells and the photosensitivity to the skin. Taking upconversion photodynamic therapy as an example we report here a biorthogonal chemistry solution to circumvent this problem. The luminescence upconversion nanoparticles (UCNPs) are anchored with one handle of click reaction and targeting entity, these nanoplatforms enable the imaging/labelling/tracking, especially for imaging-guided surgery. Once they are targeted, the photosensitizers armed with the other match handle will be injected in situ and click reaction will occur between the two handles to link the photosensitizers closely with the targeted nanoplatforms in a very short time, enabling the PDT function of the nanoplatforms. Proof of principle has been demonstrated in vitro and in vivo. This approach can be readily extended to chemotherapy, radiotherapy, etc. to overcome the side effect of these therapies of cancers.

Controlled synthesis, formation mechanism, and great enhancement of red upconversion luminescence of NaYF4:Yb3+, Er3+ nanocrystals/submicroplates at low doping level.

Strong red upconversion luminescence of rare-earth ions doped in nanocrystals is desirable for the biological/biomedical applications. In this paper, we describe the great enhancement of red upconversion emission (4F9/2 --> I15/2 transition of Er3+ ion) in NaYF4:Yb3+, Er3+ nanocrystals at low doping level, which is ascribed to the effectiveness of the multiphonon relaxation process due to the existence of citrate as a chelator and cross relaxation between Er3+ ions. The dissolution-recrystallization transformation, governing both the intrinsic crystalline phase (cubic and/or hexagonal phase) and the growth regime (thermodynamic vs kinetic), is responsible for the phase control of the NaYF4 crystals. The possible formation mechanism of the NaYF4 crystals and the role of trisodium citrate which acts as a chelating agent and shape modifier are discussed in detail. It is also found that the alpha --> beta phase transition is favored by the high molar ratio of fluoride to lanthanide and high hydrothermal temperature as well as long hydrothermal time.

Ultrastrong Absorption Meets Ultraweak Absorption: Unraveling the Energy-Dissipative Routes for Dye-Sensitized Upconversion Luminescence.

Dye sensitization is becoming a new dimension to highly improve the upconversion luminescence (UCL) of lanthanide-doped upconversion nanoparticles (UCNPs). However, there is still a lack of general understanding of the dye-UCNPs interactions, especially the confused large mismatch between the inputs and outputs. By taking dye-sensitized NaYF4:Yb/Er@NaYF4:Nd UCNPs as a model system, we not only revealed the in-depth energy-dissipative process for dye-sensitized UCL but also confirmed the first ever experimental observation of the energy back transfer (EBT) in the dye-sensitized UCL. Furthermore, this energy-dissipative EBT restricted the optimal ratio of dyes to UCNP. By unearthing all of the energy loss behind the EBT, energy transfer, and energy migration processes, this paper sheds light on the further design of effective dye-sensitized nanosystems for UCL or even downconversion luminescence.

An 800 nm driven NaErF4@NaLuF4 upconversion platform for multimodality imaging and photodynamic therapy.

Multimodality imaging-guided therapy based on lanthanide-doped upconversion nanoparticles (UCNPs) has become a trend in cancer theranostics. However, the overheating effect of 980 nm excitation in photodynamic therapy (PDT) and the difficulties in optimizing multimodality imaging integration within a single particle are still challenges. Herein, 800 nm driven NaErF4@NaLuF4 UCNPs have been explored for optimized multimodality imaging and near-infrared (NIR) triggered PDT. Our results confirmed that the optimal ∼5 nm shell thickness can well balance the enhancement of upconversion luminescence and the attenuation of energy transfer efficiency from Er3+ towards a photosensitizer, to achieve efficient production of singlet oxygen (1O2) for PDT under 800 nm excitation. Furthermore, the as-obtained NaErF4@NaLuF4 UCNPs showed effective and applicable performance for upconversion luminescence (UCL) imaging, X-ray computed tomography (CT), and high-field T2 magnetic resonance imaging (MRI). This nanomaterial can serve as an excellent theranostic agent for multimodality imaging and image-guided therapy.

Near Infrared Light Sensitive Ultraviolet-Blue Nanophotoswitch for Imaging-Guided "Off-On" Therapy.

Photoswitchable materials are important in broad applications. Recently appeared inorganic photoswitchable upconversion nanoparticles (PUCNPs) become a competitive candidate to surmount the widespread issue of the organic counterparts -photobleaching. However, current PUCNPs follow solely Yb3+/Nd3+ cosensitizing mode, which results in complex multilayer doping patterns and imperfectness of switching in UV-blue region. In this work, we have adopted a new strategy to construct Nd3+ free PUCNPs-NaErF4@NaYF4@NaYbF4:0.5%Tm@NaYF4. These PUCNPs demonstrate the superior property of photoswitching. A prominent UV-blue emission from Tm3+ is turned on upon 980 nm excitation, which can be completely turned off by 800 nm light. The quasi-monochromatic red upconversion emission upon 800 nm excitation-a distinct feature of undoping NaErF4 upconversion system-endows the PUCNPs with promising image-guided photoinduced "off-on" therapy in biomedicine. As a proof-of-concept we have demonstrated the imaging-guided photodynamic therapy (PDT) of cancer, where 800 nm excitation turns off the UV-blue emission and leaves the emission at 660 nm for imaging. Once the tumor site is targeted, excitation switching to 980 nm results in UV-blue emission and the red emission. The former is used to induce PDT, whereas the latter is to monitor the therapeutic process. Our study implies that this upconversion photoswitching material is suitable for real-time imaging and image-guided therapy under temporal and spatial control.

A SERS nano-tag-based fiber-optic strategy for in situ immunoassay in unprocessed whole blood.

Assay technologies capable of detecting biomarker concentrations in unprocessed whole blood samples are fundamental for applications in medical diagnostics. SERS nano-tags integrated fiber-optic biosensor (FOB) was realized for the first time for in situ immunoassay in whole blood. The reliability and sensitivity of this method rely, in a large extent, on the quality and properties of the SERS nano-tags. The constructed silica-coated Ag SERS nano-tags as labels were used in a rapid and specific in situ FOB immune sensor to detect alpha fetoprotein (AFP) in unprocessed blood samples. Preliminary results of in vivo and in situ dynamic observation of AFP of whole blood in wistar rat highlight the power of this new method.

One-step in situ solid-substrate-based whole blood immunoassay based on FRET between upconversion and gold nanoparticles.

Despite their general clinical applications, current fluorescence-based immunoassays are confronted with serious challenges, e.g. the advance serum/ plasma separation and the tedious washing process in current heterogeneous approaches, and aggregation of particles, low sensitivity and the narrow linear range in homogeneous approaches. In this paper, these urgent problems were solved in a novel one-step in situ immunoassay of whole blood samples by combining the traditional fluorescence resonance energy transfer (FRET) technology (between upconversion nanoparticles (UCNPs) and gold nanoparticles (GNPs)) and the solid-substrate based immunoassay technology. The low detection limits of goat IgG (gIgG) as 0.042µg/mL in buffers, 0.51µg/mL in 20-fold diluted whole blood samples and a wide linear range from 0.75µg/mL to 60µg/mL in blood samples were achieved. To the best of our knowledge, it is the first one-step in situ solid-substrate-based immunoassay of whole blood samples with large linear detection range. This development provides a promising platform for a rapid and sensitive immunoassay of various bio-molecules directly in whole blood without tedious separation, washing steps and aggregation problems.

Bcl-2 inhibitor uploaded upconversion nanophotosensitizers to overcome the photodynamic therapy resistance of cancer through adjuvant intervention strategy.

Similar to many other anticancer therapies, photodynamic therapy (PDT) also suffers from the intrinsic cancer resistance mediated by cell survival pathways. These survival pathways are regulated by various proteins, among which anti-apoptotic protein Bcl-2 plays an important role in regulation of programmed cell death and has been proved to involve in protecting against oxidative stimuli. Confronted by this challenge, we propose and validate here a novel upconversion photosensitizing nanoplatform which enables significant reduction of cancer resistance and improve PDT efficacy. The upconversion nanophotosensitizer contains the photosensitizing molecules - Zinc phthalocyanine (ZnPc) and Bcl-2 inhibitor - ABT737 small molecules, denoted as ABT737@ZnPc-UCNPs. ABT737 molecules were encapsulated, in a pH sensitive way, into the nanoplatform through Poly (ethylene glycol)-Poly (l-histidine) diblock copolymers (PEG-b-PHis). This nanosystem exhibits the superiority of sensitizing tumor cells for PDT through adjuvant intervention strategy. Upon reaching to lysosomes, the acidic environment changes the solubility of PEG-b-PHis, resulting in the burst-release of ABT737 molecules which deplete the Bcl-2 level in tumor cells and leave the tumor cells out from the protection of anti-apoptotic survival pathway in advance. Owing to the sensitization effect of ABT737@ZnPc-UCNPs, the PDT therapeutic efficiency of cancer cells can be significantly potentiated in vitro and in vivo.

Employing shells to eliminate concentration quenching in photonic upconversion nanostructure.

It is generally accepted that a lanthanide ions based upconversion material follows an activator low doping strategy (normally <3 mol%), because of the restriction of the harmful concentration quenching effect. Here, we demonstrate that this limitation can be broken in nanostructures. Simply by using an inert shell coating strategy, the concentration quenching effect for the activator (Er3+) could be eliminated and highly efficient upconversion luminescence realized in the activator fully doped nanostructure, e.g. NaErF4@NaYF4. More importantly, this novel nanostructure achieves some long-cherished desires, such as multiple-band co-excitation (∼800 nm, ∼980 nm and ∼1530 nm) and monochromic red emission. Proof-of-concept experiments are presented of the potential benefit of this structure in solar cells and anti-counterfeiting. This nanostructure offers new possibilities in realizing high upconversion emission and novel functionalities of lanthanide based nanomaterials.