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Background: In this study, we report on the synthesis, imaging, and radiosensitizing properties of ultrasmall β-NaGdF4:Yb50% nanoparticles as a multifunctional theranostic platform. The synthesized nanoparticles act as potent bimodal contrast agents with superior imaging properties compared to existing agents used for magnetic resonance imaging (MRI) and computed tomography (CT). Clonogenic assays demonstrated that these nanoparticles can act as effective radiosensitizers, provided that the nanoparticles are taken up intracellularly. Results: Our ultrasmall β-NaGdF4:Yb50% nanoparticles demonstrate improvement in T1-weighted contrast over the standard clinical MR imaging agent Gd-DTPA and similar CT signal enhancement capabilities as commercial agent iohexol. A 2 Gy dose of X-ray induced ~ 20% decrease in colony survival when C6 rat glial cells were incubated with non-targeted nanoparticles (NaGdF4:Yb50%), whereas the same X-ray dose resulted in a ~ 60% decrease in colony survival with targeted nanoparticles conjugated to folic acid (NaGdF4:Yb50%-FA). Intravenous administration of nanoparticles resulted in clearance through urine and feces within a short duration, based on the ex vivo analysis of Gd3+ ions via ICP-MS. Conclusion: These biocompatible and in vivo clearable ultrasmall NaGdF4:Yb50% are promising candidates for further evaluation in image-guided radiotherapy applications. [ABSTRACT FROM AUTHOR]

In this work, the application of near infrared (NIR)‐emitting NaYbF4:1%Tm3+@NaLuF4:30%Nd3+ core–shell nanoparticles is reported for noninvasive probing and monitoring the temperature during photopolymerization of dental materials. When excited at 808 nm, the synthesized nanoparticles emit NIR photoluminescence (PL) with two distinctive peaks at 865 and 980 nm which correspond to radiative transitions from the doped Nd3+ and Yb3+ ions, respectively. Luminescence intensity ratio between these two bands is found to vary with temperature due to temperature‐dependent electronic excitation energy transfer between Nd3+ and Yb3+ ions at the core/shell interface. This finding allows luminescence ratiometric evaluation of the in situ temperature during photopolymerization of resin cement (doped with nanoparticles) in a veneer placement procedure. In addition, the NIR emission also enables PL imaging of the distribution of the adhesive under the veneer. The results highlight that rare‐earth ions–doped nanoparticles with both excitation and emission in the NIR spectral range are advantageous for both PL‐based nanothermometry and imaging due to the reduced attenuation of NIR light by dental ceramics. [ABSTRACT FROM AUTHOR]

The tetrazole-based photoclick chemistry has provided a powerful tool to image proteins in live cells. To extend photoclick chemistry to living organisms with improved spatiotemporal control, here we report the design of naphthalene-based tetrazoles that can be efficiently activated by two-photon excitation with a 700 nm femtosecond pulsed laser. A water-soluble, cell-permeable naphthalene-based tetrazole was identified that reacts with acrylamide with the effective two-photon cross-section for the cycloaddition reaction determined to be 3.8 GM. Furthermore, the use of this naphthalene-tetrazole for real-time, spatially controlled imaging of microtubules in live mammalian cells via the fluorogenic, two-photon-triggered photoclick chemistry was demonstrated. [ABSTRACT FROM AUTHOR]

We report energy-transferring organically modified silica nanoparticles for two-photon photodynamic therapy. These nanoparticles co-encapsulate two-photon fluorescent dye nanoaggregates as an energy up-converting donor and a photosensitizing PDT drug as an acceptor. They combine two features: (i) aggregation-enhanced two-photon absorption and emission properties of a novel two-photon dye and (ii) nanoscopic fluorescence resonance energy transfer between this nanoaggregate and a photosensitizer, 2-devinyl-2-(1-hexyloxyethyl)pyropheophorbide. Stable aqueous dispersions of the co-encapsulating nanoparticles (diameter ≤ 30 nm) have been prepared in the nonpolar interior of micelles by coprecipitating an organically modified silica sol with the photosensitizer and an excess amount of the two-photon dye which forms fluorescent aggregates by phase separation from the particle matrix. Using a multidisciplinary nanophotonic approach, we show: (i) indirect excitation of the photosensitizer through efficient two-photon excited intraparticle energy transfer from the dye aggregates in the intracellular environment of tumor cells and (ii) generation of singlet oxygen and in vitro cytotoxic effect in tumor cells by photosensitization under two-photon irradiation. [ABSTRACT FROM AUTHOR]

This article reports a multidisciplinary approach to produce fluorescently labeled organically modified silica nanoparticles as a nonviral vector for gene delivery and biophotonics methods to optically monitor intracellular trafficking and gene transfection. Highly mono-dispersed, stable aqueous suspensions of organically modified silica nanoparticles, encapsulating fluorescent dyes and surface functionalized by cationic-amino groups, are produced by micellar nanochemistry. Gel-electrophoresis studies reveal that the particles efficiently complex with DNA and protect it from enzymatic digestion of DNase 1. The electrostatic binding of DNA onto the surface of the nanoparticles, due to positively charged amino groups, is also shown by intercalating an appropriate dye into the DNA and observing the Förster (fluorescence) resonance energy transfer between the dye (energy donor) intercalated in DNA on the surface of nanoparticles and a second dye (energy acceptor) inside the nanoparticles. Imaging by fluorescence confocal microscopy shows that cells efficiently take up the nanoparticles in vitro in the cytoplasm, and the nanoparticles deliver DNA to the nucleus. The use of plasmid encoding enhanced GFP allowed us to demonstrate the process of gene transfection in cultured cells. Our work shows that the nanomedicine approach, with nanoparticles acting as a drug-delivery platform combining multiple optical and other types of probes, provides a promising direction for targeted therapy with enhanced efficacy as well as for real-time monitoring of drug action. [ABSTRACT FROM AUTHOR]

A novel nanoparticle-based drug carrier for photodynamic therapy is reported which can provide stable aqueous dispersion of hydrophobic photosensitizers, yet preserve the key step of photogeneration of singlet oxygen, necessary for photodynamic action. A multidisciplinary approach is utilized which involves (i) nanochemistry in micellar cavity to produce these carriers, (ii) spectroscopy to confirm singlet oxygen production, and (iii) in vitro studies using tumor cells to investigate drug-carrier uptake and destruction of cancer cells by photodynamic action. Ultrafine organically modified silica-based nanoparticles (diameter ∼30 nm), entrapping water-insoluble photosensitizing anticancer drug 2-devinyl-2-(1-hexyloxyethyl) pyropheophorbide, have been synthesized in the nonpolar core of micelles by hydrolysis of triethoxyvinylsilane. The resulting drug-doped nanoparticles are spherical, highly monodispersed, and stable in aqueous system. The entrapped drug is more fluorescent in aqueous medium than the free drug, permitting use of fluorescence bioimaging studies. Irradiation of the photosensitizing drug entrapped in nanoparticles with light of suitable wavelength results in efficient generation of singlet oxygen, which is made possible by the inherent porosity of the nanoparticles. In vitro studies have demonstrated the active uptake of drug-doped nanoparticles into the cytosol of tumor cells. Significant damage to such impregnated tumor cells was observed upon irradiation with light of wavelength 650 nm. Thus, the potential of using ceramic-based nanoparticles as drug carriers for photodynamic therapy has been demonstrated. [ABSTRACT FROM AUTHOR]

The ability of stimuli‐responsive materials to respond to external stimuli depends on their intra‐ and intermolecular interactions, which, in turn, are governed by changes in the material composition. Here, the importance of these factors for new heat and light‐sensitive latexes of core‐shell nanoparticles is reported with the polystyrene core, the poly(N‐isopropylacrylamide) (PNIPAM) shell containing doped poly(3,4‐ethylenedioxythiophene) (PEDOT). It is found that hydrogen bonding, C═O─π aromatic, hydrophilic‐hydrophobic interactions in the shell cause conformational changes in PNIPAM similar to those occurring in the PNIPAM coil‐globule transition. Depending on the EDOT:PS@PNIPAM feed ratio and the PEDOT content in PNIPAM shells, these interactions and changes affect nanoparticle sizes and are responsible for shifting the lower critical solution temperature (LCST) of PNIPAM in the shell from 32.1 to 33.9 °C. The core‐shell morphology of nanoparticles is maintained only for latexes with EDOT feed to ≈9 wt.%. At the higher EDOT content, PNIPAM shells are destroyed. Synthesized PS@PNIPAM‐PEDOT latexes demonstrate temperature‐dependent behavior and produce a photothermal effect under NIR irradiation, which allows for a rise of their temperature above LCST. This dual stimuli (heat and light) responsiveness suggests an important possibility for these latexes to be used for drug or diagnostic agent delivery. [ABSTRACT FROM AUTHOR]

Noninvasive sonodynamic therapy (SDT) shows promise for brain glioma treatment due to deep tissue‐penetrating capabilities (>10 cm) of ultrasound and high spatial resolutions. Yet, this technique is hindered by inefficient production of reactive oxygen species (ROS), resulting from the hypoxic tumor microenvironment (TME), high level of ROS scavenger glutathione (GSH), and the inability to visualize glioma in vivo for precise treatment management and monitoring in current sonosentizers. To address these challenges, we fabricated a core‐shell heterostructure sonosensitizer (labeled as DFM), in which meso‐tetra (4‐carboxyphenyl) porphine (TCPP) porphyrin metal‐organic frameworks (MOF, PCN‐224(Fe)) serve as a porous shell to contain approved chemotherapeutics sorafenib (SRF) to effectively inhibit GSH synthesis, while NaErF4:Yb@NaLuF4 nanoparticles as the core provide TME‐responsive NIR IIb (≈1500–1800 nm) luminescence at 1525 for precise optical imaging. Coordination of Fe3+ into the macrocycle of TCPP at the MOFs shell is found to, besides triggering ferroptosis, reduce TCPP phosphorescence (23% decrease) and increase the triplet state (T1) oxygen quenching, substantially promoting the singlet oxygen generation (2.6‐fold increase). Furthermore, GSH in TME facilitates the reduction of Fe3+ to Fe2+, thereby eliminating the luminescence quenching of Fe3+ and augmenting the NIR IIb luminescence of Er3+ (5‐fold increase) for nanoagents accumulation imaging in intracranial glioma, realizing dynamical monitoring of SDT processes. Compared to control groups, in vitro and in vivo experiments confirm the effective ROS generation and results in a 6‐fold volume reduction of brain gliomas, reaching a survival rate of 80% at 30 days posttreatment. [ABSTRACT FROM AUTHOR]

Lanthanide-doped upconversion nanoparticles (UCNPs) are promising for applications as wide as biological imaging, multimodal imaging, photodynamic therapy, volumetric displays, and solar cells. Yet, the weak and narrow absorption of lanthanide ions poses a fundamental limit of UCNPs to withhold their brightness, creating a long-standing hurdle for the field. Dye-sensitized UCNPs are emerging to address this performance-limiting problem, yielding up to thousands-fold brighter luminescence than conventional UCNPs without dye sensitization. In their configuration, organic dyes with spectrally broad and intense absorption are anchored to the surface of UCNPs to harvest the excitation light energy, which is then transferred via Förster and/or Dexter mechanisms across the organic/inorganic interface to the lanthanides incorporated in UCNPs (with or devoid of a shell) to empower efficient upconversion. This tutorial review highlights recent progress in the development of dye sensitized UCNPs, with an emphasis on the theory of energy transfer, the geometric classification of the dye sensitized core and core/shell nanocrystals, and their emerging photonic and biophotonic applications. Opportunities and challenges offered by dye sensitized UCNPs are also discussed. [ABSTRACT FROM AUTHOR]

To investigate the impact of linker(s) joining the photosensitizer HPPH [3-(1’-hexyloxy) ethyl-3-devinylpyropheophorbide-a] and the cyanine dye (CD) in tumor-imaging and photodynamic therapy (dual-function agents), a series of HPPH-CD conjugates were synthesized. The modifications were done in an attempt to minimize Forster Resonance Energy Transfer (FRET) between the two chromophores and maximize singlet oxygen production. Among the conjugates containing variable length of linkers, the HPPH-CD conjugate, in which the photosensitizer (PS) and the CD was joined by four Carbon [(CH 2 ) 4 ] units showed higher tumor uptake, improved tumor contrast and limited skin uptake in mice bearing Colon-26 (BALB/c) or U87 tumors in Nude mice. The bi-functional agents in which the HPPH was linked at the meta -position of phenyl-substituted CD 5, 6 and 7 showed longer tumor response (cure) than the corresponding para -substituted analogs 2 , 3 , and 4 , which suggests that the orientation of the PS and CD moieties within the conjugate also makes a substantial difference in tumor-specificity. Compared to HPPH, the singlet oxygen yields of all the HPPH-CD conjugates were significantly low, and required a higher therapeutic dose to achieve the same in vivo response obtained by HPPH-PDT alone. However, conjugate 6 produced a higher singlet oxygen yield with reduced FRET and exhibited enhanced long-term PDT efficacy in mice bearing Colon-26 (BALB/c) and U87 tumors (nude) than its counterparts, including our lead compound (HPPH-CD), making it the most efficacious of the series. Thus, these conjugates bearing cyanine dye moiety (CD) provide an opportunity of imaging deeply seated tumors for fluorescence-guided surgery with an option of PDT. [ABSTRACT FROM AUTHOR]

The authors introduce a novel multilayer core/shell design to broadly upconvert infrared (IR) light at many discrete wavelengths into visible or near‐IR (NIR) emissions. It utilizes hexagonal‐phase core/multishell NaYF4:10%Er3+@NaYF4@NaYF4:10%Ho3+@NaYF4@NaYF4:1%Tm3+@NaYF4 nanoparticles, where the active core as well as each active shell upconvert a distinct set of IR wavelength. The inert NaYF4 layers in between these upconverting domains efficiently suppress the detrimental cross‐relaxation processes between different types of lanthanide ions, thus yielding about two times more efficient upconversion photoluminescence than the counterpart NaYF4:10%Er3+@NaYF4:10%Ho3+ @NaYF4:1%Tm3+@NaYF4 without the inert NaYF4 layers, and about one order of magnitude higher than the core/shell NaYF4:10%Er3+, 10%Ho3+, 1%Tm3+@NaYF4 nanoparticles without spatially isolating the Er3+, Ho3+, and Tm3+ ions. These core/multishell nanoparticles can be excited at ≈1120–1190 nm (due to Ho3+), ≈1190–1260 nm (due to Tm3+), and ≈1450–1580 nm (due to Er3+), collectively covering a broad spectral range of about 270 nm in the IR range that can be very useful for IR photosensitization of solar cells. [ABSTRACT FROM AUTHOR]

Light upconverting nanostructures employing lanthanide ions constitute an emerging research field recognized with wide ramifications and impact in many areas ranging from healthcare, to energy and, to security. The core–shell design of these nanostructures allows us to deliberately introduce a hierarchy of electronic energy states, thus providing unprecedented opportunities to manipulate the electronic excitation, energy transfer and upconverted emissions. The core–shell morphology also causes the suppression of quenching mechanisms to produce efficient upconversion emission for biophotonic and photonic applications. Using hierarchical architect, whereby each shell layer can be defined to have a specific feature, the electronic structure as well as the physiochemical structure of the upconverting nanomaterials can be tuned to couple other electronic states on the surface such as excitations of organic dye molecules or localized surface plasmons from metallic nanostructures, or to introduce a broad range of imaging or therapeutic modalities into a single conduct. In this review, we summarize the key aspects of nanophotonic control of the light upconverting nanoparticles through governed design and preparation of hierarchical shells in the core–shell nanostructures, and review their emerging applications in the biomedical field, solar energy conversion, as well as security encoding. [ABSTRACT FROM AUTHOR]

Background: Low-intensity light can decelerate neurodegenerative disease progression and reduce amyloid β (Aβ) levels in the cortex, though the cellular and molecular mechanisms by which photobiomodulation (PBM) protects against neurodegeneration are still in the early stages. Microglia cells play a key role in the pathology of Alzheimer's disease by causing chronic inflammation. We present new results concerning the PBM of both oxidative stress and microglia metabolism associated with the activation of metabolic processes by 808 nm near-infrared light. Methods: The studies were carried out using healthy male mice to obtain the microglial cell suspension from the hippocampus. Oligomeric β-amyloid (1-42) was prepared and used to treat microglia cells. Light irradiation of cells was performed using diode lasers emitting at 808 nm (30 mW/cm2 for 5 min, resulting in a dose of 10 J/cm2). Mitochondrial membrane potential, ROS level studies, cell viability, apoptosis, and necrosis assays were performed using epifluorescence microscopy. Phagocytosis, nitric oxide and H2O2 production, arginase, and glucose 6-phosphate dehydrogenase activities were measured using standard assays. Cytokines, glucose, lactate, and ATP were measurements with ELISA. As our data were normally distributed, two-way ANOVA test was used. Results: The light induces a metabolic shift from glycolysis to mitochondrial activity in pro-inflammatory microglia affected by oligomeric Aβ. Thereby, the level of anti-inflammatory microglia increases. This process is accompanied by a decrease in pro-inflammatory cytokines and an activation of phagocytosis. Light exposure decreases the Aβ-induced activity of glucose-6-phosphate dehydrogenase, an enzyme that regulates the rate of the pentose phosphate pathway, which activates nicotinamide adenine dinucleotide phosphate oxidases to further produce ROS. During co-cultivation of neurons with microglia, light prevents the death of neurons, which is caused by ROS produced by Aβ-altered microglia. Conclusions: These original data clarify reasons for how PBM protects against neurodegeneration and support the use of light for therapeutic research in the treatment of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Low‐level light therapy (LLLT) is emerging as a promising therapeutic approach to modulate the biochemical and molecular processes within living cells. LLLT is known to produce local and systemic effects; therefore, immune cells in local tissues or in the circulation are affected by light. However, this specific effect remains weakly explored. In this study, the effect of red (650 nm) and NIR (808 nm) light on phagocytosis (respiratory burst), cytokine expression, mitochondrial activity, ROS generation, Ca2+ influx and membrane depolarization in macrophages in vitro is investigated. Both the phagocytic capacity and adhesion of macrophages strongly (~2.5 times) increased in the first hours after exposure to light in a dose‐dependent manner. The light‐evoked upregulation of phagocytosis is found to be less efficient than the maximal pharmacologically induced enhancement of ~3.2 times. Also, red/NIR light reduces the production of pro‐inflammatory cytokines and activates the secretion of anti‐inflammatory cytokines by several times in activated macrophages. At the same time, the viability shows a biphasic dose response: it increases after irradiation with lower doses (0.3–1 J cm−2) and decreases after treatment with higher doses (18–30 J cm−2), which is apparently associated with the upregulation of ROS generation, followed by an increase in the mitochondrial activity. [ABSTRACT FROM AUTHOR]

We report herein a simple and efficient approach to the synthesis of a variety of meso-substituted purpurinimides. The reaction of meso -substituted purpurinimide with N-bromosuccinimide regioselectively introduced a bromo functionality at the 20-position, which on further reaction with a variety of boronic acids under Suzuki reaction conditions yielded the corresponding meso-substituted analogues. Interestingly, the free base and the metalated analogues showed remarkable differences in photosensitizing efficacy (PDT) and tumor-imaging ability. For example, the free-base conjugate showed significant in vitro PDT efficacy, but limited tumor avidity in mice bearing tumors, whereas the corresponding NiII derivative did not produce any cell kill, but showed excellent tumor-imaging ability at a dose of 0.3 μmol kg−1 at 24, 48, and 72 h post-injection. The limited PDT efficacy of the NiII analogue could be due to its inability to produce singlet oxygen, a key cytotoxic agent required for cell kill in PDT. Based on electrochemical and spectroelectrochemical data in DMSO, the first one-electron oxidation (0.52 V vs. SCE) and the first one-electron reduction (−0.57-0.67 V vs. SCE) of both the free base and the corresponding NiII conjugates are centered on the cyanine dye, whereas the second one-electron reduction (−0.81 V vs. SCE) of the two conjugates is assigned to the purpurinimide part of the molecule. Reduction of the cyanine dye unit is facile and occurs prior to reduction of the purpurinimide group, which suggests that the cyanine dye unit as an oxidant could be the driving force for quenching of the excited triplet state of the molecules. An interaction between the cyanine dye and the purpurinimide group is clearly observed in the free-base conjugate, which compares with a negligible interaction between the two functional groups in the NiII conjugate. As a result, the larger HOMO-LUMO gap of the free-base conjugate and the corresponding smaller quenching constant is a reason to decrease the intramolecular quenching process and increase the production of singlet oxygen to some degree. [ABSTRACT FROM AUTHOR]

Abstract: A series of thio- and selenopyrylium analogues of 2,4-di(4-dimethylaminophen-yl)-6-methylthiopyrylium iodide were prepared in five steps from 4-dimethylaminophenyl-propargyl aldehyde and the corresponding lithium acetylide. When bound to DNA, all of the dyes absorb at wavelengths >600nm, which avoids the hemoglobin band I maximum at 575nm. The binding of the series of dyes to double-stranded DNA was examined spectrophotometrically and by isothermal titration calorimetry to determine binding constants, by a topoisomerase I DNA unwinding assay, by competition dialysis with [poly(dGdC)]2 and [poly(dAdT)]2, and by ethidium bromide displacement studies to examine propensities for intercalation, and by circular dichroism studies. The dyes were found to show mixed binding modes. [Copyright &y& Elsevier]

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, which is not sensitive to radiotherapy and chemotherapy and very often experiences postoperative relapse. In this regard, effective screening of liver cancer is considered as the most important and urgent task. The aim of our study was to determine whether N-methyl-D-aspartate receptor (NMDAR) and, in particular, its subunits, can serve as biomarkers to distinguish the precancerous liver at early stages of liver fibrosis. We assessed the development of HCC after 10, 15, and 22 wk using a HCC rat model. The expression of NMDAR subunits was monitored at different stages of HCC by means of immunohistochemistry combined with epifluorescence microscopy imaging, Western blotting, and direct bisulfite sequencing. NMDAR subunits were not found in healthy liver tissues. In contrast, NMDAR subunits, in particular NR1 and NR2B, appeared at the stage of severe liver fibrosis (precancerous liver disease) in rats and were expressed during the development of HCC in rats and mice. Using the direct bisulfite sequencing, we detected that increased expression of NMDAR directly correlated with the demethylation of CpG islands in the promoter region of genes encoding receptor subunits. The obtained results confirmed that NMDAR subunits can serve as new biomarkers of precancerous liver disease, severe fibrosis, and its progression towards HCC. NEW & NOTEWORTHY We have shown NMDAR expression in cell transformation process at early stages of cancer, specifically HCC. The aim of our study was to define the disease stages from precancerous liver disease towards liver cancer progression when NMDAR subunits were expressed/detected. A fibrosis/HCC rat model, immunohistochemistry combined with epifluorescence microscopy imaging, Western blotting was used. The dynamics of appearance of NMDAR subunits, their expression and methylation status during the development of HCC were shown and discussed. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) has become one of the most worrying health conditions with no effective treatment available with the increase in population aging. A large number of clinical studies and experiments proved that photobiomodulation (PBM) had a positive effect on AD treatment. The irradiation with red and near-infrared light at a low dose can effectively reduce an accumulation of amyloid-β (Aβ) plaques in the central nervous system, relieving the symptoms of AD. This review summarizes the parameters of PBM for AD treatment studied on cells, animals, and in clinical trials, as well as the dose–effect relationship of PBM treatment for AD. The mechanisms of PBM on the cellular level, which include regulation of microglia and astrocytes that may affect Aβ plaque elimination are also discussed. [ABSTRACT FROM AUTHOR]

Hypoxia is one of the hallmarks of solid tumor, which heavily restricts the clinical cancer therapy treatments, especially for the oxygen (O 2) -dependent photodynamic therapy (PDT). Herein, an intelligent multi-layer nanostructure was developed for decreasing the O 2 -consumption and elevating the O 2 -supply simultaneously. The cell respiration inhibitor –atovaquone (ATO) molecules were reserved in the middle mesoporous silicon layer, and thus were intelligently released at the tumor site after the degradation of gatekeeper of MnO 2 layer, which effectively inhibit tumor respiration metabolism to elevate oxygen content. Meanwhile, the degradation of MnO 2 layer can generate O 2 , further boosting oxygen content. Moreover, the inner upconversion nanostructures as the near infrared (NIR) light-transducers enable to activate photosensitizers for deep-tissue PDT. Systematic experiments demonstrate that this suppressing O 2 -consumption and O 2 -generation strategy improved oxygen supply to boost the singlet oxygen generation to eradicate cancer cells under NIR light excitation. Better still, superior trimodality imaging capabilities (computed tomography (CT), NIR-II window fluorescence, and tumor microenvironment-responsive T1-weighted magnetic resonance (MR) imaging) of the nanoplatform were evaluated. Our findings offer a promising aproach to conquer the serious hypoxia problem in cancer therapy by turning down the O 2 metabolism aveneue and simultaneously generating O 2. [ABSTRACT FROM AUTHOR]

Although photobiomodulation (PBM) and gamma visual stimulatqion (GVS) have been overwhelmingly explored in the recent time as a possible light stimulation (LS) means of Alzheimer's disease (AD) therapy, their effects have not been assessed at once. In our research, the AD mouse model was stimulated using light with various parameters [continuous wave (PBM) or 40 Hz pulsed visible LED (GVS) or 40 Hz pulsed 808 nm LED (PBM and GVS treatment)]]. The brain slices collected from the LS treated AD model mice were evaluated using (i) fluorescence microscopy to image thioflavine-S labeled amy-loid-β (Aβ) plaques (the main hallmark of AD), or (ii) two-photon excited fluorescence (TPEF) imaging of unlabeled Aβ plaques, showing that the amount of Aβ plaques was reduced after LS treatment. The imaging results correlated well with the results of Morris water maze (MWM) test, which demonstrated that the spatial learning and memory abilities of LS treated mice were noticeably higher than those of untreated mice. The LS effect was also assessed by in vivo nonlinear optical imaging, revealing that the cerebral amyloid angiopathy decreased spe-cifically as a result of 40 Hz pulsed 808 nm irradiation, on the contrary, the angiopathy reversed after visible 40 Hz pulsed light treatment. The obtained results provide useful reference for further optimization of the LS (PBM or GVS) parameters to achieve efficient phototherapy of AD. • AD model mice were irradiated by visible or 808 nm light. • Visible LED at 40 Hz or 808 nm LED in continuous wave or 40 Hz modes were used. • Accumulation of Aβ peptide aggregates was reduced after light stimulation. • Cerebral amyloid angiopathy decreased specifically after 40 Hz pulsed 808 nm LED. • Learning and memory abilities of AD mice improved after all types of irradiation. [ABSTRACT FROM AUTHOR]

Red and near‐infrared (NIR) light effect on Ca2+ ions flux through the influence on N‐methyl‐D‐aspartate receptors (NMDARs) and their functioning in HeLa cells was studied in vitro. Cells were irradiated by 650 and 808 nm laser light at different power densities and doses and the obtained effect was compared with that caused by the pharmacological agents. The laser light was found to elevate Ca2+ influx into cell cytoplasm in a dose‐dependent manner without changes of the NMDAR functioning. Furthermore, the light of both wavelengths demonstrated the ability to elevate Ca2+ influx under the pharmacological blockade of NMDARs and also might partially abolish the blockade enhancing Ca2+ influx after selective stimulation of the receptors with NMDA. Simultaneously, the light at moderate doses demonstrated a photobiostimulating effect on cells. Based on our experiments and data reported in the literature, we suggest that the low‐power visible and NIR light can instigate a cell membrane depolarization via nonthermal activation, resulting in the fast induction of Ca2+ influx into cells. The obtained results also demonstrate that NIR light can be used for nonthermal and nonpharmacological stimulation of NMDARs in cancer cells. [ABSTRACT FROM AUTHOR]

The 1500–1700 nm spectral range in short wave infrared (SWIR) region allows for biological imaging with large imaging depth, high contrast and resolution. However, very few SWIR imaging probes exist, and rarely reported probes (e.g., rare‐earth‐based ones with excitation at 980 nm) are often associated with biological heating effect. Here, a class of erbium (Er3+)‐sensitized core–shell nanocrystals of NaErF4:Yb3+@NaLuF4, which emit efficient SWIR luminescence peaked at 1525 nm under 808 nm excitation, without producing any local heating, is described. The inert shell inhibits concentration‐dependent quenching and allows for an enriched incorporation of 100% Er3+ into the core, yielding about ≈650‐fold higher SWIR luminescence than parent core nanocrystals. Importantly, an appropriate doping of ytterbium (Yb3+) (optimized concentration, 20%) into the core is shown to further enhance SWIR luminescence (by twofold), endowing the nanocrystals with a high quantum yield of 11%. This Yb3+‐mediated enhancement is possibly due to the suppression of upconverting pathways and the formation of energy trapping centers that prevent the energy migration to intrinsic lattice defects. These bright SWIR core/shell nanocrystals allow high contrast in vitro imaging of HeLa cells and in vivo through‐skull imaging of blood vasculature in the mouse brain. The 1500–1700 nm spectral range in short wave infrared (SWIR) region permits biological imaging with large imaging depth, high contrast and resolution. A class of erbium (Er3+)‐sensitized core–shell nanocrystals of NaErF4:Yb3+@NaLuF4, emitting efficient SWIR luminescence at 1525 nm under 808 nm excitation, is designed and synthesized, allowing to demonstrate high contrast luminescence bioimaging in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Plasmon-enhanced luminescence (PEL) is a unique photophysical phenomenon in which the interaction between luminescent moieties and metal nanostructures results in a marked luminescence enhancement. PEL offers several advantages and has been extensively used to design robust biosensing platforms for luminescence-based detection and diagnostics applications, as well as for the development of many efficient bioimaging platforms, enabling high-contrast non-invasive real-time optical imaging of biological tissues, cells, and organelles with high spatial and temporal resolution. This review summarizes recent progress in the development of various PEL-based biosensors and bioimaging platforms for diverse biological and biomedical applications. Specifically, we comprehensively assessed rationally designed PEL-based biosensors that can efficiently detect biomarkers (proteins and nucleic acids) in point-of-care tests, highlighting significant improvements in the sensing performance upon the integration of PEL. In addition to discussing the merits and demerits of recently developed PEL-based biosensors on substrates or in solutions, we include a brief discussion on integrating PEL-based biosensing platforms into microfluidic devices as a promising multi-responsive detection method. The review also presents comprehensive details about the recent advances in the development of various PEL-based multi-functional (passive targeting, active targeting, and stimuli-responsive) bioimaging probes, highlighting the scope of future improvements in devising robust PEL-based nanosystems to achieve more effective diagnostic and therapeutic insights by enabling imaging-guided therapy. [Display omitted] • Plasmon-enhanced luminescence (PEL) can be employed in biosensing and bioimaging. • PEL biosensors are developed both on substrate and in solutions. • Integration of PEL biosensors into microfluidic devices is described. • Biological tissues and cells can be labeled and imaged using PEL probes. • PEL probes can target areas of interests and be activated by external stimuli. [ABSTRACT FROM AUTHOR]

We introduce a hybrid organic-inorganic system consisting of epitaxial NaYF4:Yb3+/X3+@NaYbF4@NaYF4:Nd3+ (X = null, Er, Ho, Tm, or Pr) core/shell/shell (CSS) nanocrystal with organic dye, indocyanine green (ICG) on the nanocrystal surface. This system is able to produce a set of narrow band emissions with a large Stokes-shift (>200 nm) in the second biological window of optical transparency (NIR-II, 1000-1700 nm), by directional energy transfer from light-harvesting surface ICG, via lanthanide ions in the shells, to the emitter X3+ in the core. Surface ICG not only increases the NIR-II emission intensity of inorganic CSS nanocrystals by ~4-fold but also provides a broadly excitable spectral range (700-860 nm) that facilitates their use in bioapplications. We show that the NIR-II emission from ICG-sensitized Er3+-doped CSS nanocrystals allows clear observation of a sharp image through 9 mm thick chicken breast tissue, and emission signal detection through 22 mm thick tissue yielding a better imaging profile than from typically used Yb/Tm-codoped upconverting nanocrystals imaged in the NIR-I region (700-950 nm). Our result on in vivo imaging suggests that these ICG-sensitized CSS nanocrystals are suitable for deep optical imaging in the NIR-II region. [ABSTRACT FROM AUTHOR]

We report herein the synthesis and biological efficacy of near-infrared (NIR), bacteriochlorin analogues: 3-(1′-butyloxy)ethyl-3-deacetyl-bacteriopurpurin-18-N-butylimide methyl ester (3) and the corresponding carboxylic acid 10. In in vitro assays, compared to its methyl ester analogue 3, the corresponding carboxylic acid derivative 10 showed higher photosensitizing efficacy. However, due to drastically different pharmacokinetics in vivo, the PS 3 (HPLC purity >99%) showed higher tumor uptake and long-term tumor cure than 10 (HPLC purity >96.5%) in BALB/c mice bearing Colon 26 tumors. Isomerically pure R- and S- isomers of 3 (3a and 3b, purity by HPLC > 99%) under similar treatment parameters showed identical efficacy in vitro and in vivo. In addition, photosensitizer (PS) 3 showed limited skin phototoxicity and provides an additional advantage over the clinically approved chemically complex hematoporphyrin derivative as well as other porphyrin-based PDT agents, which makes 3 a promising dual-function agent for fluorescence-guided surgery with an option of phototherapy of cancer. [ABSTRACT FROM AUTHOR]

This paper introduces the concept of in-situ upconversion of deep penetrating near infrared light via second harmonic generation from ZnO nanocrystals delivered into cells to effect photo activated therapies, such as photodynamic therapy, which usually require activation by visible light with limited penetration through biological tissues. We demonstrated this concept by subcellular activation of a photodynamic therapy drug, Chlorin e6, excited within its strong absorption Soret band by the second harmonic (SH) light, generated at 409 nm by ZnO nanocrystals, which were targeted to cancer cells and internalized through the folate-receptor mediated endocytosis. By a combination of theoretical modeling and experimental measurements, we show that SH light, generated in-situ by ZnO nanocrystals significantly contributes to activation of photosensitizer, leading to cell death through both apoptotic and necrotic pathways initiated in the cytoplasm. This targeted photodynamic action was studied using label-free Coherent Anti-Stokes Raman Scattering imaging of the treated cells to monitor changes in the distribution of native cellular proteins and lipids. We found that initiation of photodynamic therapy with upconverted light led to global reduction in the intracellular concentration of macromolecules, likely due to suppression of proteins and lipids synthesis, which could be considered as a real-time indicator of cellular damage from photodynamic treatment. In prospective applications this in-situ photon upconversion could be further extended using ZnO nanocrystals surface functionalized with a specific organelle targeting group, provided a powerful approach to identify and consequently maximize a cellular response to phototherapy, selectively initiated in a specific cellular organelle. [ABSTRACT FROM AUTHOR]

T lymphocytes play a central role in many human immunologic disorders, including autoimmune and alloimmune diseases. In hematopoietic stem cell transplantation, acute graft-versus-host-disease (GVHD) is caused by an attack on the recipient's tissues from donor allogeneic T cells. Selectively depleting GVHD-causing cells prior to transplant may prevent GVHD. In this study, we evaluated 24 chalcogenorhodamine photosensitizers for their ability to selectively deplete reactive T lymphocytes and identified the photosensitizer 2-Se-Cl, which accumulates in stimulated T cells in proportion to oxidative phosphorylation. The photosensitizer is also a potent stimulator of P-glycoprotein (P-gp). Enhanced P-gp activity promotes the efficient removal of photosensitizer not sequestered in mitochondria and protects resting lymphocytes that are essential for antipathogen and antitumor responses. To evaluate the selective depletion of alloimmune responses, donor C57BL/6 splenocytes were cocultured for 5 d with irradiated BALB/c splenocytes and then photodepleted (PD). PD-treated splenocytes were infused into lethally irradiated BALB/c (sameparty) or C3H/HeJ (third-party) mice. Same-party mice that received PD-treated splenocytes at the time of transplant lived 100 d without evidence of GVHD. In contrast, all mice that received untreated primed splenocytes and third-party mice that received PD-treated splenocytes died of lethal GVHD. To evaluate the preservation of antiviral immune responses, acute lymphocytic choriomeningitis virus infection was used. After photodepletion, expansion of Ag-specific naive CD8+ T cells and viral clearance remained fully intact. The high selectivity of this novel photosensitizer may have broad applications and provide alternative treatment options for patients with T lymphocyte-mediated diseases. [ABSTRACT FROM AUTHOR]

We examined two selenorhodamines with amide and thioamide functionality at the 5-position of a 9-(2-thienyl) substituent on the selenoxanthylium analogue of the Texas-red core for their potential as photosensitizers for photodynamic therapy (PDT) in P-glycoprotein (P-gp)-expressing Colo-26 cells. These compounds were examined for their photophysical properties (absorption, fluorescence, and ability to generate singlet oxygen), for their uptake into Colo-26 cells in the absence or presence of verapamil, for their dark and phototoxicity toward Colo-26 cells, and for their co-localization with mitochondrial-specific agents in Colo-26 cells. Both compounds were extremely effective photosensitizers with values of EC 50 ⩽ 4 × 10 −8 M toward Colo-26 cells with 1.0 J cm −2 laser light delivered at 630 ± 2 nm. [ABSTRACT FROM AUTHOR]

Photonic nanomaterials have found wide applications in theranostics. We introduce here a design of all-organic photonic nanoparticles, different from traditional ones, in which we utilize nanoblend of a low-bandgap π-conjugated polymer (LB-CP) and polystyrene as the photonic core, surrounded by an FDA-approved polymeric surfactant. This design provides capability for efficient deep tissue imaging using highly penetrating near-infrared (NIR) excitation and emission of LB-CP and also allows us to incorporate a NIR phosphorescent oxygen-sensitive dye in the core to serve as a dual-emissive probe for hypoxia imaging. These biophotonic nanoblend (BNB) particles (∼20 nm in diameter) show facile blood circulation, efficient disease targeting and minimal liver filtration as well as sustained renal excretion in the intravenously administered mouse models, as noninvasively visualized by the NIR emission signals. In diseased mouse models, pathological tissue deoxygenation at hypoxic sites was successfully detected with ratiometric spectral information. We also show that our nanoformulation exhibits no apparent toxicity, thus serving as a versatile biophotonics platform for diagnostic imaging. [ABSTRACT FROM AUTHOR]

Weexamined a series of selenorhodamines with amide and thioamidefunctionality at the 5-position of a 9-(2-thienyl) substituent onthe selenorhodamine core for their potential as photosensitizers forphotodynamic therapy (PDT) in P-glycoprotein (P-gp) expressing cells.These compounds were examined for their photophysical properties (absorption,fluorescence, and ability to generate singlet oxygen), for their uptakeinto Colo-26 cells in the absence or presence of verapamil, for theirdark and phototoxicity toward Colo-26 cells, for their rates of transportin monolayers of multidrug-resistant, P-gp-overexpressing MDCKII-MDR1cells, and for their colocalization with mitochondrial specific agentsin Colo-26 cells. Thioamide derivatives 16band 18bwere more effective photosensitizers than amide derivatives 15band 17b. Selenorhodamine thioamides 16band 18bwere useful in a combination therapyto treat Colo-26 cells in vitro: a synergistic therapeutic effect was observed when Colo-26 cellswere exposed to PDT and treatment with the cancer drug doxorubicin. [ABSTRACT FROM AUTHOR]

Analoguesof Texas red incorporating the heavy chalcogens S, Se,and Te atoms in the xanthylium core were prepared from the additionof aryl Grignard reagents to appropriate chalcogenoxanthone precursors.The xanthones were prepared via directed metalation of amide precursors,addition of dichalcogenide electrophiles, and electrophilic cyclizationof the resulting chalcogenides with phosphorus oxychloride and triethylamine.The Texas red analogues incorporate two fused julolidine rings containingthe rhodamine nitrogen atoms. Analogues containing two “half-julolidine”groups (a trimethyltetrahydroquinoline) and one julolidine and one“half-julolidine” were also prepared. The photophysicsof the Texas red analogues were examined. The S-analogues were highlyfluorescent, the Se-analogues generated single oxygen (1O2) efficiently upon irradiation, and the Te-analogueswere easily oxidized to rhodamines with the telluroxide oxidationstate. The tellurorhodamine telluroxides absorb at wavelengths ≥690nm and emit with fluorescence maxima >720 nm. A mesityl-substitutedtellurorhodamine derivative localized in the mitochondria of Colo-26cells (a murine colon carcinoma cell line) and was oxidized in vitroto the fluorescent telluroxide. [ABSTRACT FROM AUTHOR]

Several 9-aryl-3,6-diaminotelluroxanthyliumdyes withphenyl, 2-methylphenyl, and 2,4,6-trimethylphenyl substituents atthe 9-position were prepared. The characterization of these compoundsincluded determination of 125Te NMR spectra, fluorescencequantum yields (ΦF), and quantum yields for the generationof singlet oxygen [Φ(1O2)]. While thesecompounds were essentially nonfluorescent (ΦF<0.005), they produce 1O2with Φ(1O2) between 0.43 and 0.90. The tellurorosamines were oxidizedwith 1O2via self-photosensitization to thecorresponding telluroxides, which allowed their preparation free ofexcess oxidant. Telluroxides with a 9-(2-methylphenyl) or 9-(2,4,6-trimethylphenyl)substituent were fluorescent with quantum yields for fluorescencebetween 0.20 and 0.31. Steric bulk at the 9-position of the resultingtelluroxides impacted rates of inter- and intramolecular attack ofnucleophiles and stability of the telluroxide in aqueous media nearphysiological pH. The yield of reduction of the telluroxide with glutathionewas also dependent on the steric bulk of the 9-aryl substituent. Thestructure of products from oxidation of the 9-(4-bromophenyl) tellurorosaminewas determined by X-ray crystallography and indicated the additionof oxygen nucleophiles to the 9-position of the telluroxide oxidationstate of the tellurorosamine. [ABSTRACT FROM AUTHOR]

Irradiation with red or near-infrared (NIR) light in low level light therapy (LLLT) is found to stimulate cellular processes and bioenergetics, resulting in enhanced wound healing, pain control, neurodegenerative diseases treatment, etc. During light irradiation of tissues and organs, different cells are affected, though the connection between photostimulation of cells and their environmental conditions remains poorly understood. In this report, red/NIR light-stimulated angiogenesis is investigated using endothelial cells in vitro, with a focus on the capillary-like structure (CLS) formation and the respective biochemical processes in cells under conditions proximate to a healthy or malignant environment, which strongly defines angiogenesis. To model environmental conditions for endotheliocytes in vitro, the cell culture environment was supplemented by an augmented conditioned medium from macrophages or cancer cells. The biochemical processes in endothelial cell cultures were investigated with and without irradiation by red (650 nm) and near-infrared (808 nm) laser diodes and under normoxia or hypoxia conditions. A light-stimulated angiogenesis has been found, with a more efficient stimulation by 650 nm light compared to 808 nm light. It was shown that the irradiation with light promoted extracellular Ca2+ influx, fostered cell cycle progression, proliferation and NO generation in endothelial cells, and caused an increase in vascular endothelial growth factor (VEGF) production by endothelial cells and M2 macrophages under hypoxia conditions. The activation of VEGF production by macrophages was found to be associated with an increase in the number of M2 macrophages after light irradiation under hypoxia conditions. Thus, a new pathway of an activation of the endothelial cell metabolism, which is related with the extracellular Ca2+ influx after light irradiation, has been revealed. Red/NIR light-stimulated angiogenesis has been studied using endothelial cells in vitro, with focus on CLS formation and the respective biochemical processes in cell models proximate to a healthy or malignant environment. A light-stimulated angiogenesis has been found, stimulated via extracellular Ca2+ influx, cell cycle progression, proliferation and NO generation, VEGF production increase by endothelial cells under hypoxia conditions. [Display omitted] • Red and near-infrared light stimulates angiogenesis in vitro, with more efficient stimulation at 650 nm than 808 nm. • The irradiation promotes Ca ion influx, cell cycle progression, proliferation, and NO generation in endothelial cells. • The irradiation increases VEGF production by endothelial cells and macrophages under hypoxia. • An increase in VEGF production is associated with a rise in the number of M2 macrophages after irradiation under hypoxia. • A new activation pathway of endothelial cell metabolism, which is related to light-induced Ca ion influx, is revealed. [ABSTRACT FROM AUTHOR]

We describe and demonstrate a general strategy for engineering binary and ternary hybrid nanoparticles based on spontaneous epitaxial nucleation and growth of a second and third component onto seed nanoparticles in high-temperature organic solutions. Multifunctional hybrid nanoparticles that combine magnetic, plasmonic, and semiconducting properties and that are tunable in size and morphology can be realized, as demonstrated for combinations of Au, Fe3O4, and PbS or PbSe. The properties of each component within the hybrids can be modulated strongly by the conjugating component(s) aided by the coherent interfaces between them. [ABSTRACT FROM AUTHOR]

Abstract: Several thio and seleno analogues of tetramethylrosamine (TMR) were prepared. Thio derivatives of TMR have absorption maxima near 570nm, while seleno derivatives of TMR have absorption maxima near 580nm. The 3- or 4-N,N-dimethylaminophenyl substituent in the 9-position greatly increases internal conversion, which lowers quantum yields for fluorescence and the generation of singlet oxygen. Thio and seleno analogues of TMR are effective photosensitizers against chemosensitive AUXB1 cells in vitro and against multidrug-resistant CR1R12 cells in vitro, which have been treated with verapamil. The CR1R12 cells accumulated significantly lower concentrations of the photosensitizers relative to the AUXB1 cells presumably due to the expression of P-glycoprotein (Pgp) in the CR1R12 cells. Following treatment with 5×10−5 M verapamil, the uptake in CR1R12 cells of several fluorescent thio analogues of TMR is comparable to that observed for the chemosensitive AUXB1 cells. [Copyright &y& Elsevier]

Abstract: 21,23-Dithiaporphyrins (2–10) were designed and prepared as analogues of 5,20-diphenyl-10,15-bis(4-carboxylatomethoxy)phenyl-21,23-dithiaporphyrin (1) to examine the impact of steric bulk at the 5- and 20-meso positions as well as the impact of symmetry. Changes at the meso positions had minimal impact on the UV–vis–near-IR absorption spectra, quantum yields for the generation of singlet oxygen, and quantum yields for fluorescence and some impact on values of the octanol/water partition coefficient. Of the compounds 1–10, 5-phenyl-20-(2-thienyl)-10,15-bis-(4-carboxylatomethoxy-phenyl)-21,23-dithiaporphyrin (3) showed the greatest phototoxicity toward cultured R3230AC cells, with 68% cell kill at 1×10−7M and irradiation with 5Jcm−2 of 350–750nm light. Results in this study suggest that smaller substituents on the meso ring and less symmetrical compounds are more effective as photosensitizers than compounds with two bulky substituents at adjoining meso sites and a higher symmetry. The mitochondria appear to be involved in the process of phototoxicity as determined by the inhibition of whole cell cytochrome c oxidase activity in cells treated with 3 and light. No impact upon mitochondrial cytochrome c oxidase activity was observed in cells treated with 3 and no light. Fluorescence microscopy studies suggest that the mitochondria are not initial sites of accumulation of 3. [Copyright &y& Elsevier]

Magneto-plasmonic nanocomposites can possess properties inherent to both individual components (iron oxide and gold nanoparticles) and are reported to demonstrate high potential in targeted drug delivery and therapy. Herein, we report on Fe3O4/Au magneto-plasmonic nanocomposites (MPNC) synthesized with the use of amino acid tryptophan via chemical and photochemical reduction of Au ions in the presence of nanosized magnetite. The magnetic field (MF) induced aggregation was accompanied by an increase in the absorption in the near-infrared (NIR) spectral region, which was demonstrated to provide an enhanced photothermal (PT) effect under NIR laser irradiation (at 808 nm). A possibility for therapeutic application of the MPNC was illustrated using cancer cells in vitro. Cultured HeLa cells were treated by MPNC in the presence of MF and without it, following laser irradiation and imaging using confocal laser scanning microscopy. After scanning laser irradiation of the MPNC/MF treated cells, a formation and rise of photothermally-induced microbubbles on the cell surfaces was observed, leading to a damage of the cell membrane and cell destruction. We conclude that the synthesized magneto-plasmonic Fe3O4/Au nanosystems exhibit magnetic field-induced reversible aggregation accompanied by an increase in NIR absorption, allowing for an opportunity to magnetophoretically control and locally enhance a NIR light-induced thermal effect, which holds high promise for the application in photothermal therapy. [ABSTRACT FROM AUTHOR]

• An all graphene quantum dot FRET probe was designed and constructed. • The green emitting graphene quantum dot was used as donor and the red emitting graphene quantum dot was used as acceptor. • The GQD-FRET probe was used to detect the HE4 ovarian cancer biomarker. • The ratoimetric GQD-FRET probe was able to detect as low as 4.8 pM, with a large dynamic range of 4 pM to 300 nM. Ovarian cancer (OVC), the most lethal form of all gynecological cancers, is a big threat to women's health. Late diagnosis at the advanced stages is one of the major reasons for the ovarian cancer-related deaths. Conventionally, the up-regulated proteins CA125 (cancer antigen 125) and HE4 (human epididymis protein 4) are used as biomarkers to diagnose the OVC malignancies. The lack of sensitivity/specificity and the false-positive results create complexity in the diagnostic process. With specificity over 90 %, HE4 is suitable for diagnosing ovarian cancer. Herein, we have developed an ultrasensitive all-graphene quantum dot (GQD) Förster resonance energy transfer (FRET) probe for the ratiometric detection of HE4 biomarker. A set of two GQD samples were solvothermally prepared and then analyzed by the morphological, structural, and photophysical characterization. One GQD sample exhibited a strong green emission, peaked at around 515 nm, while the other GQD sample displayed a strong red emission with maximum at around 615 nm. The good spectral overlap between the emission and excitation spectra of the green and red GQDs, respectively, all allowed us to consider them for the design of FRET-based probe. The green and red-emitting GQDs were conjugated with HE4 antibody and used as donor and acceptor, respectively for the ratiometric sensing of HE4 ovarian cancer biomarker. The all GQD FRET probe was able to detect as low as 4.8 pM, along with a large dynamic detection range up to 300 nM. The selectivity and interference effect of the developed FRET probe was also investigated against different protein combinations. [ABSTRACT FROM AUTHOR]

Low level light therapy uses light of specific wavelengths in red and near-infrared spectral range to treat various pathological conditions. This light is able to modulate biochemical cascade reactions in cells that can have important health implications. In this study, the effect of low intensity light at 650, 808 and 1064 nm on neurons and two types of cancer cells (neuroblastoma and HeLa) is reported, with focus on the photoinduced change of intracellular level of Ca2+ ions and corresponding signaling pathways. The obtained results show that 650 and 808 nm light promotes intracellular Ca2+ elevation regardless of cell type, but with different dynamics due to the specificities of Ca2+ regulation in neurons and cancer cells. Two origins responsible for Ca2+ elevation are determined to be: influx of exogenous Ca2+ ions into cells and Ca2+ release from endoplasmic reticulum. Our investigation of the related cellular processes shows that light-induced membrane depolarization is distinctly involved in the mechanism of Ca2+ influx. Ca2+ release from endoplasmic reticulum activated by reactive oxygen species generation is considered as a possible light-dependent signaling pathway. In contrast to the irradiation with 650 and 808 nm light, no effects are observed under 1064 nm irradiation. We believe that the obtained insights are of high significance and can be useful for the development of drug-free phototherapy. Unlabelled Image • 650 and 808 nm light increases level of Ca2+ in neurons and cancer cells in vitro. • In contrast, no effect is observed under 1064 nm irradiation. • Intracellular influx and release of Ca2+ from endoplasmic reticulum are the causes. • Ca2+ influx is distinctly associated with light-driven membrane depolarization. • Crosstalk between light-induced ROS and endoplasmic reticulum Ca2+ release is studied. [ABSTRACT FROM AUTHOR]

In this paper, we report an approach to polymerization of a nanocomposite containing UV-polymerizable organic material and inorganic, NaYbF4:Tm3+ core-based nanoparticles (NPs), which are optimized for upconversion of near infrared (NIR) to ultraviolet (UV) and blue light. Our approach is compatible with numerous existing UV-polymerizable compositions and the NaYF4: Yb, Tm3+ core-based NPs are much more stable against harsh conditions than NIR organic photo-initiators proposed earlier. The use of a core-shell design for the NPs can provide a suitable method for binding with organic constituents of the nanocomposite, while maintaining efficient NIR-to-UV/blue conversion in the NaYbF4 core. The prepared photopolymerized transparent polymer nanocomposites display upconversion photoluminescence in UV, visible and NIR ranges. We also demonstrate a successful fabrication of polymerized nanocomposite structure with millimeter/submillimeter size uniformly patterned by 980 nm irradiation of inexpensive laser diode through a photomask. [ABSTRACT FROM AUTHOR]

A nanosized drug complex was explored to improve the efficiency of cancer chemotherapy, complementing it with nanodelivery and photodynamic therapy. For this, nanomolar amounts of a non-covalent nanocomplex of Doxorubicin (Dox) with carbon nanoparticle C60 fullerene (C60) were applied in 1:1 and 2:1 molar ratio, exploiting C60 both as a drug-carrier and as a photosensitizer. The fluorescence microscopy analysis of human leukemic CCRF-CEM cells, in vitro cancer model, treated with nanocomplexes showed Dox's nuclear and C60's extranuclear localization. It gave an opportunity to realize a double hit strategy against cancer cells based on Dox's antiproliferative activity and C60's photoinduced pro-oxidant activity. When cells were treated with 2:1 C60-Dox and irradiated at 405 nm the high cytotoxicity of photo-irradiated C60-Dox enabled a nanomolar concentration of Dox and C60 to efficiently kill cancer cells in vitro. The high pro-oxidant and pro-apoptotic efficiency decreased IC50 16, 9 and 7 × 103-fold, if compared with the action of Dox, non-irradiated nanocomplex, and C60's photodynamic effect, correspondingly. Hereafter, a strong synergy of therapy arising from the combination of C60-mediated Dox delivery and C60 photoexcitation was revealed. Our data indicate that a combination of chemo- and photodynamic therapies with C60-Dox nanoformulation provides a promising synergetic approach for cancer treatment. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a minimally invasive cancer modality that combines a photosensitizer (PS), light, and oxygen. Introduction of new nanotechnologies holds potential to improve PDT performance. Upconversion nanoparticles (UCNPs) offer potentially advantageous benefits for PDT, attributed to their distinct photon upconverting feature. The ability to convert near-infrared (NIR) light into visible or even ultraviolet light via UCNPs allows for the activation of nearby PS agents to produce singlet oxygen, as most PS agents absorb visible and ultraviolet light. The use of a longer NIR wavelength permits light to penetrate deeper into tissue, and thus PDT of a deeper tissue can be effectively achieved with the incorporation of UCNPs. Recent progress in UCNP development has generated the possibility to employ a wide variety of NIR excitation sources in PDT. Use of UCNPs enables concurrent strategies for loading, targeting, and controlling the release of additional drugs. In this review article, recent progress in the development of UCNPs for PDT applications is summarized. [ABSTRACT FROM AUTHOR]

This article presents a study on singlet oxygen generation via two-photon excited flourescence resonance energy transfer. Among many possible applications, compounds capable of generating singlet oxygen following efficient two-photon absorption (TPA) could broaden the applicability of singlet oxygen generation. Porphyrin sensitizers have low TPA cross sections, limiting their usefulness in two-photon absorption applications. This limitation has stimulated interest in the discovery of porphyrins with enhanced TPA cross sections through chemical modification of the porphyrin chromophore.