In situ observation of thermal-driven structural transitions of a ß-NaYF4 single nanoparticle aided with correlative cathodoluminescence electron microscopy.

NaYF4 systems have been widely studied as up-conversion host matrices, and their phase transitions are flexible and worth investigating in great detail. Herein, the evolution of morphology and crystal structure of a Eu3+-doped ß-NaYF4 single nanoparticle heated in an air atmosphere was investigated using in situ transmission electron microscopy (TEM). The annealing process revealed that the hexagonal ß-NaYF4 phase undergoes sequential transformations into high-temperature cubic phases at both 350 °C and 500 °C. The emission characteristics of Eu3+ in the single nanoparticle after heating treatment were also analyzed using Correlative Cathodoluminescence Electron Microscopy (CCLEM). The results of CCLEM suggest a gradual decrease followed by a subsequent increase in structural symmetry. A comprehensive spectroscopic and structural analysis encapsulates the entire transformation process as NaYF4 → YOF → Y2O3. In situ energy dispersive spectroscopy analyses (EDS) support this reaction process. The aforementioned technique yields correlative lattice-resolved TEM images and nanoscale spectroscopic information, which can be employed to assess the structure-function relationships on the nanoscale.

Bridging the Buried Interface with Piperazine Dihydriodide Layer for High Performance Inverted Solar Cells.

Given that it is closely related to perovskite crystallization and interfacial trap densities, buried interfacial engineering is crucial for creating effective and stable perovskite solar cells. Compared with the in-depth studies on the defect at the top perovskite interface, exploring the defect of the buried side of perovskite film is relatively complicated and scanty owing to the non-exposed feature. Herein, the degradation process is probed from the buried side of perovskite films with continuous illumination and its effects on morphology and photoelectronic characteristics with a facile lift-off method. Additionally, a buffer layer of Piperazine Dihydriodide (PDI2 ) is inserted into the imbedded bottom interface. The PDI2 buffer layer is able to lubricate the mismatched thermal expansion between perovskite and substrate, resulting in the release of lattice strain and thus a void-free buried interface. With the PDI2 buffer layer, the degradation originates from the growing voids and increasing non-radiative recombination at the imbedded bottom interfaces are suppressed effectively, leading to prolonged operation lifetime of the perovskite solar cells. As a result, the power conversion efficiency of an optimized p-i-n inverted photovoltaic device reaches 23.47% (with certified 23.42%) and the unencapsulated devices maintain 90.27% of initial efficiency after 800 h continuous light soaking.

Rinsing Intermediate Phase Strategy for Modulating Perovskite Crystal Growth and Fabricating Highly Efficient and Stable Inverted Solar Cells.

During the fabrication of metal halide perovskite films, polycrystal growth and maturation are largely influenced by high-temperature annealing. However, this process would cause crystals to expand or contract at various depths in the film, leading to microscopic structural deformation and further altering the optoelectronic properties of the perovskite film. Herein, we propose an additional rinsing intermediate phase (RIP) strategy that involves precovering the perovskite film surface with a mixed organic layer prior to high-temperature annealing. The lattice distortion of the microscopic structure brought on by the driving force of the heat field is greatly reduced as a result of the modulation for the upper surface of the intermediate phase film by the rinse layer. This strategy can prepare films with high crystallinity, minor residual stresses, fewer defects, and overall film uniformity. As a result, the modified inverted perovskite solar cell (PSC) achieves a certified power conversion (PCE) of 22.76%. Meanwhile, since the rinse layer is involved in the entire crystal formation process, ion migration and buildup in the device are prevented between the interface. Consequently, the devices still retain 90% of their initial PCE, demonstrating enhanced operational stability after 500 h of operation. This method of modulating the intermediate perovskite state offers an investigation into improving the traditional method of making thin films, which is anticipated to hasten the commercialization of perovskite photovoltaics.

Skin-safe nanophotosensitizers with highly-controlled synthesized polydopamine shell for synergetic chemo-photodynamic therapy.

Although photodynamic therapy (PDT) has been extensively studied as an established modality of cancer treatment, it still suffers from a few clinical limitations, such as skin phototoxicity and tumor hypoxia. To circumvent these hurdles, hollow silica mesoporous nanoparticles (HMSNs) loaded with photosensitizers were employed as the nanoplatform to construct multifunctional nanoparticles (NPs). Specifically, an ultra-uniform polydopamine (PDA) shell was highly controlled grown around HMSNs by photogenerated outwards-diffused 1O2, followed by conjugation of folic acid-poly(ethylene glycol) and chelation of Fe2+ ions. Thanks to the optimal thickness of light-absorbing PDA shell, the multifunctional NPs exhibited not only negligible skin phototoxicity but also efficient 1O2 generation and photothermal (PT)-enhanced •OH generation upon respective photoirradiation. Anti-tumor therapy was then performed on both 4 T1 tumor cells and tumor-bearing mice by the combination of 638 nm PDT and 808 nm PT-enhanced chemodynamic therapy (CDT). As a result, high therapeutic efficacy was achieved compared to single-modality therapy, with a cell inhibitory rate of 86% and tumor growth inhibition of 70.4% respectively. More interestingly, tumor metastasis was effectively inhibited by the synergetic treatment. These results convincingly demonstrate that our multifunctional NPs are very promising skin-safe PDT agents combined with CDT for efficient tumor therapy.

Optimization of a SnO2-Based Electron Transport Layer Using Zirconium Acetylacetonate for Efficient and Stable Perovskite Solar Cells.

SnO2 is a promising material for use as an electron transfer layer (ETL) in perovskite photovoltaic devices due to its suitable energy level alignment with the perovskite, high electron mobility, excellent optical transmission, and low-temperature processability. The development of high-quality SnO2 ETLs with a large coverage and that are pinhole-free is crucial to enhancing the performance and stability of the perovskite solar cells (PSCs). In this work, zirconium acetylacetonate (ZrAcac) was introduced to form a double-layered ETL, in which an ideal cascade energy level alignment is obtained. The surface of the resulting ZrAcac/SnO2 (Zr-SnO2) layer is compact and smooth and had a high coverage of SnO2, which enhances the electron extractability, improves ion blocking, and reduces the charge accumulation at the interface. As a result, the fill factor (FF, 80.99%), power conversion efficiency (PCE, 22.44%), and stability of the Zr-SnO2 device have been significantly improved compared to PSCs with only a SnO2 ETL. In addition, the PCE of the Zr-SnO2 device is maintained at more than 80% of the initial efficiency after 500 h of continuous illumination.

A Comprehensive Study of Drug Loading in Hollow Mesoporous Silica Nanoparticles: Impacting Factors and Loading Efficiency.

Although hollow mesoporous silica nanoparticles (HMSNs) have been intensively studied as nanocarriers, selecting the right HMSNs for specific drugs still remains challenging due to the enormous diversity in so far reported HMSNs and drugs. To this end, we herein made a comprehensive study on drug loading in HMSNs from the viewpoint of impacting factors and loading efficiency. Specifically, two types of HMSNs with negative and positive zeta potential were delicately constructed, and three categories of drugs were selected as delivery targets: highly hydrophobic and lipophobic (oily), hydrophobic, and hydrophilic. The results indicated that (i) oily drugs could be efficiently loaded into both of the two HMSNs, (ii) HMSNs were not good carriers for hydrophobic drugs, especially for planar drugs, (iii) HMSNs had high loading efficiency towards oppositely charged hydrophilic drugs, i.e., negatively charged HMSNs for cationic molecules and vice versa, (iv) entrapped drugs would alter zeta potential of drug-loaded HMSNs. This work may provide general guidelines about designing high-payload HMSNs by reference to the physicochemical property of drugs.

Secondary Grain Growth in Organic-Inorganic Perovskite Films with Ethylamine Hydrochloride Additives for Highly Efficient Solar Cells.

The grain boundaries of perovskite polycrystalline are regarded as a defect region that not only provides carrier recombination sites but also introduces device degradation pathways. Efforts to enlarging the grain size of a perovskite film and reducing its grain boundary are crucial for highly efficient and stable perovskite solar cells (PSCs). Some effective methods that facilitate grain growth are postdeposition thermal annealing and solvent vapor annealing. However, a detailed understanding of grain growth mechanisms in perovskite films is lacking. In this study, perovskite films were prepared by adding ethylamine hydrochloride (EACl) to the precursor solution. This additive strategy promotes a new grain growth mode, secondary grain growth, in perovskite films. Secondary grain growth leads to much larger grains with a high crystallographic orientation. These excellent properties lead to reduced grain boundaries and the densities of boundary defects. The improved film quality results in a prolonged charge-carrier lifetime and a significantly enhanced power conversion efficiency (PCE). Compared with the 18.42% PCE of the control device, the PCE of the device with EACl additives reaches 21.07%.

Luminescent ruthenium(II)-containing metallopolymers with different ligands: synthesis and application as oxygen nanosensor for hypoxia imaging.

A series of Ru(II)-containing metallopolymers with different polypyridyl complexes, namely [Ru(N^N)2(L)](PF6)2 (L = bipyridine-branched polymer; N^N = bpy: 2,2'-bipyridine (Ru 1); phen: 1,10-phenanthroline (Ru 2); dpp: 4,7-diphenyl-1,10-phenanthroline (Ru 3)), were synthesized with the motive that adjusting π-conjugation length of ligands might produce competent luminescent oxygen probes. The three hydrophobic metallopolymers were studied with 1H NMR, UV-Vis absorption, and emission spectroscopy, and then were utilized to prepare biocompatible nanoparticles (NPs) via a nanoprecipitation method. Luminescent properties of the NPs were investigated against dissolved oxygen by steady-state and time-resolved spectroscopy respectively. Luminescence quenching of the three NPs all followed a linear behavior in the range of 0-43 ppm (oxygen concentration), but Ru 3-NPs exhibited the highest oxygen sensitivity (82%) and longest emission wavelength (λex = 460 nm; λem = 617 nm). In addition, external interferons from cellular environments (e.g., pH, temperature, and proteins) had been studied on Ru 3-NPs. Finally, dissolved oxygen in monolayer cells under normoxic/hypoxic conditions was clearly differentiated by using Ru 3-NPs as the luminescent sensor, and, more importantly, hypoxia within multicellular tumor spheroids was vividly imaged. These results suggest that such Ru(II)-containing metallopolymers are strong candidates for luminescent nanosensors towards hypoxia. Graphical abstract.

Facile synthesis of fluorinated nanophotosensitizers with self-supplied oxygen for efficient photodynamic therapy.

Tumor hypoxia severely reduces the efficiency of photodynamic therapy (PDT) through the insufficient supply of oxygen. In this work, we reported on a design of fluorinated nanophotosensitizers (NPSs) prepared by a facile reprecipitation-encapsulation method, with the aim of addressing the issue of hypoxia. The fluorinated NPSs consisted of a hybrid particle core of perfluorosiloxane-polystyrene, doped with a fluorinated photosensitizer, and a biocompatible poly-l-lysine shell. Compared with non-fluorinated counterpart NPSs that are similarly prepared except for the replacement of perfluorosiloxane with alkoxysilane, the fluorinated NPSs saturated with O2 exhibit approximately 3.5 fold higher singlet oxygen production yield and higher in vitro PDT efficiency due to the O2-carrying capability of intra-particle 'F-C' bonds.

Highly Stable and Luminescent Oxygen Nanosensor Based on Ruthenium-Containing Metallopolymer for Real-Time Imaging of Intracellular Oxygenation.

Metal complex-based luminescent oxygen nanosensors have been intensively studied for biomedical applications. In terms of monitoring dynamics of intracellular oxygen, however, high-quality nanosensors are still badly needed, because of stringent requirements on stability, biocompatibility and luminescence intensity, aside from oxygen sensitivity. In this paper, we reported a type of highly luminescent and stable oxygen nanosensors prepared from metallopolymer. First, a novel ruthenium(II)-containing metallopolymer was synthesized by chelating the oxygen probe [Ru(bpy)3]2+ with a bipyridine-branched hydrophobic copolymer, which was then doped into polymeric nanoparticles (NPs) by a reprecipitation method, followed by further conjugation to selectively target mitochondria (Mito-NPs). The resultant Mtio-NPs possessed a small hydrodynamic size of ∼85 nm, good biocompatibility and high stability resulting from PEGylation and stable nature of Ru-complex. Because the complexed [Ru(bpy)3]2+ homogeneously resided on particle surface, Mito-NPs exhibited strong luminescence at 608 nm that was free of aggregation-caused-quenching, the utmost oxygen sensitivity of free [Ru(bpy)3]2+ probe ( Q = 75%), and linear Stern-Volmer oxygen luminescence quenching plots. Taking advantage of the mitochondria-specific nanosensors, intracellular oxygenation and deoxygenation processes were real-time monitored for 10 min by confocal luminescence imaging, visualized by the gradual weakening (by more than 90%) and enhancing (by 50%) of the red emission, respectively.

A fluorescent nanoprobe for real-time monitoring of intracellular singlet oxygen during photodynamic therapy.

Sensing of intracellular singlet oxygen (1O2) is required in order to optimize photodynamic therapy (PDT). An optical nanoprobe is reported here for the optical determination of intracellular 1O2. The probe consists of a porous particle core doped with the commercial 1O2 probe 1,3-diphenylisobenzofuran (DPBF) and a layer of poly-L-lysine. The nanoparticle probes have a particle size of ~80 nm in diameter, exhibit good biocompatibility, improved photostability and high sensitivity for 1O2 in both absorbance (peak at 420 nm) and fluorescence (with excitation/emission peaks at 405/458 nm). Nanoprobes doped with 20% of DPBF are best suited even though they suffer from concentration quenching of fluorescence. In comparison with the commercial fluorescent 1O2 probe SOSG, 20%-doped DPBF-NPs (aged) shows higher sensitivity for 1O2 generated at an early stage. The best nanoprobes were used to real-time monitor the PDT-triggered generation of 1O2 inside live cells, and the generation rate is found to depend on the supply of intracellular oxygen. Graphical abstract A fluorescent nanoprobe featured with refined selectivity and improved sensitivity towards 1O2 was prepared from the absorption-based probe DBPF and used to real-time monitoring of the generation of intracellular 1O2 produced during PDT.

Preparation of Fluorescent Dye-Doped Biocompatible Nanoparticles for Cell Labeling.

In this paper, we report a series of fluorescent biocompatible nanoparticles (NPs), prepared by a facile reprecipitation-encapsulation method, for cellular labeling. The as-prepared NPs exhibit a narrow size distribution of 70-110 nm, and a core-shell structure comprised of a hybrid core doped with different dyes and a poly-L-lysine (PLL) shell. With coumarin 6, nile red, and meso- tetraphenylporphyrin as the imaging agents, the fluorescent NPs gave green, orange, and red emissions respectively. Due to the positively charged PLL shell, the fluorescent NPs exhibit neglected cytotoxicity and efficient cellular uptake. After incubation with living cells, the results obtained by laser confocal microscope from green, orange, and red channels all clearly show that the fluores- cent NPs are inhomogenously localized inside the cytoplasm without penetrating into the nucleus. Since such PLL-modified NPs can encapsulate other hydrophobic dyes, a wide spectrum of nanoimaging agents is thus expected. Furthermore, the surface amino groups on the PLL shell afford an anchoring site for further bioconjugation, and targeted imaging is also very promising.

Intracellular Temperature Imaging in Gold Nanorod-Assisted Photothermal Therapy with Luminescent Eu(III) Chelate Nanoparticles.

Eu-tris(dinaphthoylmethane)-bis-(trioctylphosphine oxide) (Eu-DT) molecules encapsulated by Polystyrene and bis(trimethoxysilyl)decane nanoparticles were prepared via a modified encapsulation-reprecipitation method and show a high sensitivity to sense temperature. After surface modification with poly-L-lysine, the fluorescent nanoparticles obtained a well biocompatibility and low toxicity at a certain concentration. In the physiological temperature range (25-45 °C), the fluorescence of the nanoparticles is rather sensitive to temperature with a sensitivity of -2.6%/°C. The temperature nanosensors and gold nanorods were internalized into living HepG2 cells. The fluorescence intensity of phagocytic nanoparticles decreased with the irradiation of 808-nm laser, which were captured by Epi-fluorescence microscope.

Synthesis and Near-infrared Luminescent Properties of NaGdF4:Nd3+@NaGdF4 Core/Shell Nanocrystals with Different Shell Thickness.

The near-infrared to near-infrared (NIR-to-NIR) photoluminescence of nanocrystals has outstanding advantages in biological imaging. NaGdF4:Nd3+ core nanocrystals and NaGdF4:Nd3+@NaGdF4 core/shell nanocrystals with different shell thicknesses were synthesized by a simple solvothermal method. The obtained nanocrystals were characterized by transmission electron microscopy (TEM) and X-ray diffraction (XRD) analysis. The phase of all nanocrystals is hexagonal. NaGdF4:Nd3+ core nanocrystals have an average size of 6 nm. By controlling core-shell ratio for 1:2 and 1:3, we obtained NaGdF4:Nd3+@NaGdF4 core/shell nanocrystals with average sizes of 10 nm and 11 nm, respectively. When excited at 808 nm, strong NIR emission was observed. The emission peaks at -860 nm, -1060 nm and -1330 nm correspond to the transitions from the 4F3/2 state to the 4I9/2, 4I1/2 and 4I13/2 state of Nd3+ ions, respectively. The emission intensity of NaGdF4:Nd3+@NaGdF4 core/shell nanocrystals is stronger than that of the core. The intensity increases with the increase of shell thickness. The shell improves the luminous efficiency by reducing surface defects. The decay time of Nd3+ emission in NaGdF4:Nd3+@NaGdF4 core/shell nanocrystal is longer than that in NaGdF4:Nd3+ core, indicating that the shell isolates effectively the emitting ions (Nd3+) from the quenching defects. With the increase of shell thickness, the decay time becomes longer. Within a certain range of shell thickness, thicker shell can protect the emitting Nd3+ ions on the surface of core nanocrystals more effectively.

Sensitive detection of PDT-induced cell damages with luminescent oxygen nanosensors.

In this work luminescent nanosensors specifically created for intracellular oxygen (ic-O2) were utilized to assess photodynamic therapy (PDT) -induced cell damages. Firstly, ic-O2 was demonstrated to be consumed much faster than extracellular O2 with respective O2 nanosensors. Using the ic-O2 nanosensors, PDT-treated cells with different degree of impairment were then resolved according to the oxygen consumption rate (OCR). The evolving trend of cytotoxicity derived from OCRs was in agreement with cell viability obtained from 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Moreover, the direct damage of PDT on cell mitochondria was successfully detected by monitoring respiration instantly after PDT treatment, which is actually beyond the scope of MTT assay. These results suggest that fluorescence sensing of ic-O2-associated cell respiration is promising and even may become a standardized method, complementary to MTT assay, to evaluate PDT-induced cytotoxicity.

Synthesis and optimization of ZnPc-loaded biocompatible nanoparticles for efficient photodynamic therapy.

Zinc(ii) phthalocyanine (ZnPc) is a promising photosensitizer for PDT but suffers from aggregation in a physiological aqueous environment. In this paper, a class of biocompatible polymeric nanoparticles (NPs) was prepared to encapsulate ZnPc molecules. Mostly because of the planar structure, ZnPc molecules were difficult to be encapsulated into the polymeric NPs unless further coated with a thick poly-l-lysine (PLL) layer. The PLL shell endowed the NPs with good biocompatibility, efficient cellular uptake, and potential bioconjugation. The degree of aggregation (DOA) of ZnPc molecules in PLL-NPs was thoroughly investigated based on self-defined relative DOA, and a loading capacity of 4 wt% was deduced as the turning point for aggravating aggregation. Similarly, the optimal loading capacity of ZnPc was determined to be 4% according to the 1O2 generation rate, demonstrating the feasibility of the DOA approach. Polymers with large rigid units (PVK and PFO) were also utilized to relieve the aggregation of ZnPc in NPs. Taking advantage of the optimized ZnPc-loaded NPs, high PDT efficacy was demonstrated in HepG2 cells and in tumor-bearing mice as well. Both high in vitro and in vivo PDT efficacy and biocompatibility are demonstrated. Aside from affording a class of efficient biocompatible nanophotosensitizers, this work is also instructive to design other types of ZnPc-based nanocarriers, in which aggregation should be well considered.

A Pyrene@Micelle Sensor for Fluorescent Oxygen Sensing.

For most fluorescent oxygen sensors developed today, their fabrication process is either time-consuming or needs specialized knowledge. In this work, a robust fluorescent oxygen sensor is facilely constructed by dissolving pyrene molecules into CTAB aqueous solution. The as-prepared pyrene@micelle sensors have submicron-sized diameter, and the concentration of utilized pyrene can be reduced as low as 0.8 mM but still can exhibit dominant excimer emission. The excimer fluorescence is sensitive to dissolved oxygen in both intensity and lifetime, and the respective Stern-Volmer plot follows a nonlinear behavior justified by a two-site model. Because of the merits of large Stokes shift (~140 nm), easy fabrication, and robustness, the pyrene@micelle sensors are very attractive for practical determination of oxygen.

Targetable phosphorescent oxygen nanosensors for the assessment of tumor mitochondrial dysfunction by monitoring the respiratory activity.

Cellular respiration is a worthwhile criterion to evaluate mitochondrial dysfunction by measuring the dissolved oxygen. However, most of the existing sensing strategies merely report extracellular (ec-) or intracellular (ic-) O2 rather than intramitochondrial (im-) O2 . Herein we present a method to assess tumor mitochondrial dysfunction with three phosphorescent nanosensors, which respond to ec-, ic-, and im-O2 . Time-resolved luminescence is applied to determine the respective oxygen consumption rates (OCRs) under varying respiratory conditions. Data obtained for the OCRs and on (intra)cellular O2 gradients demonstrate that mitochondria in tumor cells are distinctly less active than those of healthy cells, resulting from restrained glucose utilization of and physical injury to the mitochondria. We believe that such a site-resolved sensing strategy can be applied to numerous other situations, for example to evaluate the adverse effects of drug candidates.

Poly-l-lysine assisted synthesis of core-shell nanoparticles and conjugation with triphenylphosphonium to target mitochondria.

In this paper, we report a facile route to synthesize mitochondria-targeted core-shell nanoparticles (NPs). Firstly, PLL-coated NPs are prepared by a one-step reprecipitation-encapsulation method assisted by positively charged poly-l-lysine (PLL). The effect of the molecular weight of PLL on the formation of particles is studied in terms of morphology, size and zeta potential, and medium-sized PLL (MH-PLL) is proved to be the optimum one. By means of crosslinking with different amounts of glutaraldehyde, amino groups in MH-PLL-NPs are characterized by zeta potential and fluorescamine assay, respectively. The results indicate that in the PLL shell, only a small portion of amino groups (surface amino groups, SAGs) are available for conjugation, while the other groups exclusively contribute to zeta potential. Subsequently, a known mitochondriotropic ligand, triphenylphosphonium (TPP), is conjugated with SAG via a carbodiimide reaction, which is evaluated by NMR and absorption spectra, respectively. The TPP-MH-PLL-NPs exhibit a low cytotoxic effect tested by the MTT method, as well as efficient cellular uptake microscopically observed after a fluorescent dye, coumarin 6, is incorporated. Most importantly, the TPP-conjugated NPs can selectively target mitochondria, demonstrated by the merged z-stacked images in co-localization experiments with MitoTracker-stained mitochondria. Given that many hydrophobic species could be loaded into the particle core, TPP-MH-PLL-NPs are very promising as mitochondria-targeted nanocarriers for imaging or anti-cancer therapies.

Electron transfer process between Ce3+ donor and Yb3+ acceptor levels in the bandgap of Y3Al5O12 (YAG).

Thermoluminescence (TL) properties of Ce(3+) and Yb(3+) co-doped in Y(3)Al(5)O(12) (YAG) were studied with the aim of determining the location of energy levels of Ce(3+) and Yb(2+) relative to the bottom of the conduction band (CB) and the top of the valence band (VB) of YAG. The TL glow peak at about 180 °C when heating rate ß = 1°C s(-1) was assigned to electron release from Yb(2+), indicating that Yb(3+) acts as an electron trap. The trap depth, which is the depth of the ground-state level of Yb(2+) below the bottom of the CB, was derived from the temperatures of the maximum of the TL glow peak at different heating rates. The value is, within the experimental and theoretical uncertainties, in good agreement with that derived from the O(2-) --> Yb(3+) charge transfer energy. Thermoluminescence excitation spectroscopy (TLES) was used to establish the location of energy levels of Ce(3+). From the derived data the energy level diagram of YAG:Ce(3+), Yb(3+) is constructed and possible electron transfer processes are discussed.