NIR-Driven Water Splitting H2 Production Nanoplatform for H2-Mediated Cascade-Amplifying Synergetic Cancer Therapy.

As a newly emerging treatment strategy for many diseases, hydrogen therapy has attracted a lot of attention because of its excellent biosafety. However, the high diffusivity and low solubility of hydrogen make it difficult to accumulate in local lesions. Herein, we develop a H2 self-generation nanoplatform by in situ water splitting driven by near-infrared (NIR) laser. In this work, core-shell nanoparticles (CSNPs) of NaGdF4:Yb,Tm/g-C3N4/Cu3P (UCC) nanocomposites as core encapsulated with zeolitic imidazolate framework-8 (ZIF-8) modified with folic acid as shell are designed and synthesized. Due to the acid-responsive ZIF-8 shell, enhanced permeability and retention (EPR) effect, and folate receptor-mediated endocytosis, CSNPs are selectively captured by tumor cells. Upon 980 nm laser irradiation, CSNPs exhibit a high production capacity of H2 and active oxygen species (ROS), as well as an appropriate photothermal conversion temperature. Furthermore, rising temperature increases the Fenton reaction rate of Cu(I) with H2O2 and strengthens the curative effect of chemodynamic therapy (CDT). The excess glutathione (GSH) in tumor microenvironment (TME) can deplete positive holes produced in the valence band of g-C3N4 in the g-C3N4/Cu3P Z-scheme heterojunction. GSH also can reduce Cu(II) to Cu(I), ensuring a continuous Fenton reaction. Thus, a NIR-driven H2 production nanoplatform is constructed for H2-mediated cascade-amplifying multimodal synergetic therapy.

NaGdF4:Yb,Er-Ag nanowire hybrid nanocomposite for multifunctional upconversion emission, optical imaging, MRI and CT imaging applications.

The effect of novel silver nanowire encapsulated NaGdF4:Yb,Er hybrid nanocomposite on the upconversion emission and bioimaging properties has been investigated. The upconvension nanomaterials were synthesised by polyol method in the presence of ethylene glycol, PVP and ethylenediamine. The NaGdF4:Yb,Er-Ag hybrid was formed with upconverting NaGdF4:Yb,Er nanoparticles of size ~ 80 nm and silver nanowires of thickness ~ 30 nm. The surface plasmon induced by the silver ion in the NaGdF4:Yb,Er-Ag nanocomposite resulted an intense upconversion green emission at 520 nm and red emission at 660 nm by NIR diode laser excitation at 980 nm wavelength. The UV-Vis-NIR spectral absorption at 440 nm and 980 nm, the intense Raman vibrational modes and the strong upconversion emission results altogether confirm the localised surface plasmon resonance effect of silver ion in the hybrid nanocomposite. MRI study of both NaGdF4:Yb,Er nanoparticle and NaGdF4:Yb,Er-Ag nanocomposite revealed the T1 relaxivities of 22.13 and 10.39 mM-1 s-1, which are larger than the commercial Gd-DOTA contrast agent of 3.08 mM-1 s-1. CT imaging NaGdF4:Yb,Er-Ag and NaGdF4:Yb,Er respectively showed the values of 53.29 HU L/g and 39.51 HU L/g, which are higher than 25.78 HU L/g of the CT contrast agent Iobitridol. The NaGdF4:Yb,Er and NaGdF4:Yb,Er-Ag respectively demonstrated a negative zeta potential of 54 mV and 55 mV, that could be useful for biological application. The in vitro cytotoxicity of the NaGdF4:Yb,Er tested in HeLa and MCF-7 cancer cell line by MTT assay demonstrated a cell viability of 90 and 80 %, respectively. But, the cell viability of NaGdF4:Yb,Er-Ag slightly decreased to 80 and 78%. The confocal microscopy imaging showed that the UCNPs are effectively up-taken inside the nucleolus of the cancer cells, and it might be useful for NIR laser-assisted phototherapy for cancer treatment. Graphical abstract.

Poly(selenoviologen)-Assembled Upconversion Nanoparticles for Low-Power Single-NIR Light-Triggered Synergistic Photodynamic and Photothermal Antibacterial Therapy.

The development of a highly effective photosensitizer (PS) that can be activated with a low-power single light is a pressing issue. Herein, we report a PS for synergistic photodynamic and photothermal therapy constructed through self-assembly of poly(selenoviologen) on the surface of core-shell NaYF4:Yb/Tm@NaYF4 upconversion nanoparticles. The hybrid UCNPs/PSeV PS showed strong ROS generation ability and high photothermal conversion efficiency (∼52.5%) under the mildest reported-to-date irradiation conditions (λ = 980 nm, 150 mW/cm2, 4 min), leading to a high efficiency in killing methicillin-resistant Staphylococcus aureus (MRSA) both in vitro and in vivo. Remarkably, after intravenous injection, the reported PS accumulated preferentially in deep MRSA-infected tissues and achieved an excellent therapeutic index. This PS design realizes a low-power single-NIR light-triggered synergistic phototherapy and provides a simple and versatile strategy to develop safe clinically translatable agents for efficient treatment of deep tissue bacterial inflammations.

Selective Decoating-Induced Activation of Supramolecularly Coated Toxic Nanoparticles for Multiple Applications.

In spite of the rapid emergence of numerous nanoparticles (NPs) for biomedical applications, it is often challenging to precisely control, or effectively tame, the bioactivity/toxicity of NPs, thereby exhibiting limited applications in biomedical areas. Herein, we report the construction of hyaluronic acid (HA)-laminated, otherwise toxic methylviologen (MV), NPs via ternary host-guest complexation among cucurbit[8]uril, trans-azobenzene-conjugated HA, and MV-functionalized polylactic acid NPs (MV-NPs). The high, nonspecific toxicity of MV-NPs was effectively shielded (turned off) by HA lamination, as demonstrated in cells, zebrafish, and mouse models. The supramolecular host-guest interaction-mediated HA coating offered several HA-MV-NP modalities, including hyaluronidase locally and photoirradiation remotely, to precisely remove HA lamination on demand, thereby endowing materials with the capability of selective decoating-induced activation (DIA) for applications as a user-friendly herbicide, a selective antibacterial agent, or an anticancer nanomedicine. This work offers facile supramolecular coating and DIA strategies to effectively tame and precisely control the bioactivity and toxicity of functional nanomaterials for diverse applications.

Activatable Photodynamic Therapy with Therapeutic Effect Prediction Based on a Self-correction Upconversion Nanoprobe.

Though emerging as a promising therapeutic approach for cancers, the crucial challenge for photodynamic therapy (PDT) is activatable phototoxicity for selective cancer cell destruction with low "off-target" damage and simultaneous therapeutic effect prediction. Here, we design an upconversion nanoprobe for intracellular cathepsin B (CaB)-responsive PDT with in situ self-corrected therapeutic effect prediction. The upconversion nanoprobe is composed of multishelled upconversion nanoparticles (UCNPs) NaYF4:Gd@NaYF4:Er,Yb@NaYF4:Nd,Yb, which covalently modified with an antenna molecule 800CW for UCNPs luminance enhancement under NIR irradiation, photosensitizer Rose Bengal (RB) for PDT, Cy3 for therapeutic effect prediction, and CaB substrate peptide labeled with a QSY7 quencher. The energy of UCNPs emission at 540 nm is transferred to Cy3/RB and eventually quenched by QSY7 via two continuous luminance resonance energy transfer processes from interior UCNPs to its surface-extended QSY7. The intracellular CaB specifically cleaves peptide to release QSY7, which correspondingly activates RB with reactive oxygen species (ROS) generation for PDT and recovers Cy3 luminance for CaB imaging. UCNPs emission at 540 nm remains unchanged during the peptide cleavage process, which is served as an internal standard for Cy3 luminance correction, and the fluorescence intensity ratio of Cy3 over UCNPs (FI583/FI540) is measured for self-corrected therapeutic effect prediction. The proposed self-corrected upconversion nanoprobe implies significant potential in precise tumor therapy.

Self-Sufficient and Highly Efficient Gold Sandwich Upconversion Nanocomposite Lasers for Stretchable and Bio-applications.

Multifunctional lanthanide-doped upconversion nanoparticles (UCNPs) have spread their wings in the fields of flexible optoelectronics and biomedical applications. One of the ongoing challenges lies in achieving UCNP-based nanocomposites, which enable a continuous-wave (CW) laser action at ultralow thresholds. Here, gold sandwich UCNP nanocomposites [gold (Au1)-UCNP-gold (Au2)] capable of exhibiting lasing at ultralow thresholds under CW excitation are demonstrated. The metastable energy-level characteristics of lanthanides are advantageous for creating population inversion. In particular, localized surface plasmon resonance-based electromagnetic hotspots in the nanocomposites and the huge enhancement of scattering coefficient for the formation of coherent closed loops due to multiple scattering facilitate the process of stimulated emissions as confirmed by theoretical simulations. The nanocomposites are subjected to stretchable systems for enhancing the lasing action (threshold ∼ 0.06 kW cm-2) via a light-trapping effect. The applications in bioimaging of HeLa cells and antibacterial activity (photothermal therapy) are demonstrated using the newly designed Au1-UCNP-Au2 nanocomposites.

Na2SiF6:Cu,P: a new OSL phosphor for the radiation dosimetric applications.

A new Cu,P-doped, sodium fluorosilicate-based optically stimulated luminescence (OSL) phosphor is developed. This phosphor shows good OSL properties, and the sensitivity is comparable with that of the commercial Al(2)O(3):C (Landauer, Inc.) phosphor. For the luminescence averaged over initial 1 s, blue-stimulated luminescence and green-stimulated luminescence sensitivities were found to be 0.76 and 3.8 times, respectively, of Al(2)O(3):C (Landauer, Inc.) with 28 % of post-irradiation fading in 3 days and nil thereafter. The simple preparation procedure, fast decay, very good sensitivity and moderate fading will make this phosphor suitable for radiation dosimetry, using OSL.

Topical laser application enhances enamel fluoride uptake and tribological properties.

Topical fluoride treatment prevents dental caries. However, the resulting calcium-fluoride-like deposits are soft and have poor wear resistance; therefore, frequent treatment is required. Lasers quickly heat surfaces and can be made portable and suitable for oral remedies. We examined the morphology, nanohardness, elastic modulus, nanowear, and fluoride uptake of fluoride-treated enamel followed by CO2 laser irradiation for 5 and 10 sec, respectively. We found that laser treatments significantly increased the mechanical properties of the calcium-fluoride-like deposits. The wear resistance of the calcium-fluoride-like deposits improved about 34% after laser irradiation for 5 sec and about 40% following irradiation for 10 sec. We also found that laser treatments increased fluoride uptake by at least 23%. Overall, laser treatment significantly improved fluoride incorporation into dental tissue and the wear resistance of the protective calcium-fluoride layer.

Diode laser irradiation and fluoride uptake in human teeth.

AIM: To evaluate chemically the effects of diode laser on fluoride uptake before and after laser irradiation of enamel surfaces. METHODS: Crowns of 20 sound human teeth were halved and a 3 x 3 mm acid-resistant varnish uncovered window left for: A) no treatment; B) fluoride (Elmex gel); C) diode (fluoride + diode laser); D) diode (diode laser + fluoride). The dental surfaces were analysed using a fluoride ion-selective electrode, in order to evaluate the fluoride treatment in combination with a diode laser. Also, to investigate laser-induced compositional changes (contents in F(-)) in enamel before/after laser irradiation and topical fluoride application. RESULTS: The mean ± SD of fluoride uptake of teeth of group A was 1.55 ± 0.89 mg/l. Mean fluoride uptake increased sevenfold after fluoride gel treatment: 10.51 ± 3.38 mg/l for group B, up to 15 times after gel and laser treatment: 23.62 ± 3.58 mg/l for group C and was 22.7 ± 4.60 mg/l for group D (diode laser before fluoride application). The Kruskal Wallis test indicated a statistically significant effect of fluoride uptake for all three treatments (p<0.001). The Student-Newman-Keuls multiple comparison test indicated a statistically significant increase of fluoride uptake before and after all treatments, and also a statistically significant difference for laser treatment versus fluoride gel. However, there was no statistically significance difference between laser groups. CONCLUSIONS: There is an enhanced capability of lasers to increase fluoride uptake of enamel and providing protection to enamel surface from acid attack.

Experimental investigation of the 100 keV X-ray dose response of the high-temperature thermoluminescence in LiF:Mg,Ti (TLD-100): theoretical interpretation using the unified interaction model.

The dose response of LiF:Mg,Ti (TLD-100) chips was measured from 1 to 50,000 Gy using 100 keV X rays at the European Synchroton Radiation Facility. Glow curves were deconvoluted into component glow peaks using a computerised glow curve deconvolution (CGCD) code based on first-order kinetics. The normalised dose response, f(D), of glow peaks 4 and 5 and 5b (the major components of composite peak 5), as well as peaks 7 and 8 (two of the major components of the high-temperature thermoluminescence (HTTL) at high levels of dose) was separately determined and theoretically interpreted using the unified interaction model (UNIM). The UNIM is a nine-parameter model encompassing both the irradiation/absorption stage and the thermally induced relaxation/recombination stage with an admixture of both localised and delocalised recombination mechanisms. The effects of radiation damage are included in the present modelling via the exponential removal of luminescent centres (LCs) at high dose levels. The main features of the experimentally measured dose response are: (i) increase in f(D)(max) with glow peak temperature, (ii) increase in D(max) (the dose level at which f(D)(max) occurs) with increasing glow peak temperature, and (iii) decreased effects of radiation damage with increasing glow peak temperature. The UNIM interpretation of this behaviour requires both strongly decreasing values of ks (the relative contribution of localised recombination) as a function of glow peak temperature and, as well, significantly different values of the dose-filling constants of the trapping centre (TC) and LC for peaks 7 and 8 than those used for peaks 4 and 5. This suggests that different TC/LC configurations are responsible for HTTL. The relative intensity of peak 5a (a low-temperature satellite of peak 5 arising from localised recombination) was found to significantly increase at higher dose levels due to preferential electron and hole population of the trapping/recombination complex giving rise to composite glow peak 5. It is also demonstrated that possible changes in the trapping cross section of the LC and the competitive centres due to increasing sample/glow peak temperature do not significantly influence these observations/conclusions.

Long-term fade study of the DT-702 LiF: Mg,Cu,P TLD.

LiF thermoluminescent dosemeters (TLDs) are used by the US Navy to record radiation exposure of personnel. The Model DT-648 LiF:Mg,Ti TLD has been replaced by a new Model DT-702 LiF:Mg,Cu,P TLD. The DT-648 was used for many years and has undergone extensive testing to identify its pre- and post-irradiation fade operating characteristics. Studies have shown that the addition of copper increases the thermoluminesence sensitivity of the TLD for improved low-level radiation monitoring. This study evaluates various fading characteristics of the new copper-doped dosemeter using current equipment for processing of TLDs and calibrating to a National Institute of Standards and Technology standard source. The 57-week study took place at the Naval Dosimetry Center, Bethesda, MD, USA. TLDs were stored for various lengths of time before and after being exposed to a National Institute of Standards and Technology calibrated radiation sources. TLDs were then processed using current US Navy instructions and the resulting dose compared with the calibrated exposure. Both loss of signal and loss of sensitivity were evaluated. The results of this study have shown that the DT-702 TLD has no statistically significant change in sensitivity or change in signal with up to 57 weeks of pre- or post-irradiation time. The results of this study will increase the accuracy of exposure record keeping for the Navy and will allow longer issue periods. This will increase flexibility with international and domestic shipping procedures, as well as reduce workload requirements for dosimetry processing.

Comparison of the TL responses of two different preparations of LiF:Mg,Cu,P irradiated by photons of various energies.

The aim of this work is to present the results concerning the photon irradiation of a new phosphor, the LiF:Mg,Cu,P+PTFE, produced at the Instituto Nacional de Investigaciones Nucleares (ININ-Mexico). The photon irradiations were performed using X-rays of 16, 24, 34.5, 42, 100 and 145keV, and gamma rays from (137)Cs (662keV) and from (60)Co (1 252keV). The results obtained are normalized to the (60)Co response. The experimental data are then compared to those obtained using the commercial dosimeters TLD-100 and GR-200A.

Determination of LiF:Mg,Ti and LiF:Mg,Cu,P TL efficiency for X-rays and their application to Monte Carlo simulations of dosemeter response.

The simulation of response of a new passive area dosemeter for measuring ambient dose equivalent H*(10) for photons has been performed using the Monte Carlo code MCNP and experimentally determined responses of LiF:Mg,Ti and LiF:Mg,Cu,P thermoluminescent (TL) detectors for hard-filtered X-ray spectra from 20 to 300 keV and for 137Cs and 60Co gamma radiation. Relative TL efficiency for both types of detectors, determined in experiments with bare detectors and similar Monte Carlo simulations, compared favourably with prediction of microdosimetric models for proposed microdosimetric target sizes in the range of 20-40 nm. The concluding verification experiment showed small deviations between measured and simulated dosemeter energy response values in the range of a few percent.

The application of LiF:Mg,Cu,P to large scale personnel dosimetry: current status and future directions.

LiF:Mg,Cu,P is starting to replace LiF:Mg,Ti in a variety of personnel dosimetry applications. LiF:Mg,Cu,P has superior characteristics as compared to LiF:Mg,Ti including, higher sensitivity, improved energy response for photons, lack of supralinearity and insignificant fading. The use of LiF:Mg,Cu,P in large scale dosimetry programs is of particular interest due to the extreme sensitivity of this material to the maximum readout temperature, and the variety of different dosimetry aspects and details that must be considered for a successful implementation in routine dosimetry. Here we discuss and explain the various aspects of large scale LiF:Mg,Cu,P based dosimetry programs including the properties of the TL material, new generation of TLD readers, calibration methodologies, a new generation of dose calculation algorithms based on the use of artificial neural networks and the overall uncertainty of the dose measurement. The United States Navy (USN) will be the first US dosimetry processor who will use this new material for routine applications. Until June 2002, the Navy used two types of thermoluminescent materials for personnel dosimetry, CaF2:Mn and LiF:Mg,Ti. A program to upgrade the system and to implement LiF:Mg,Cu,P, started in the mid 1990s and was recently concluded. In 2002, the new system replaced the LiF:Mg,Ti and is scheduled to start replacing the CaF2:Mn system in 2006. A pilot study to determine the dosimetric performance of the new LiF:Mg,Cu,P based dosimetry system was recently completed, and the results show the new system to be as good or better than the current system in all areas tested. As a result, LiF:Mg,Cu,P is scheduled to become the primary personnel dosimeter for the entire US Navy in 2006.

Kinetic study of the thermoluminescence of KMgF3:LaF3 compounds employing the general one trap model.

The parameters characterising the trap centres involved in the thermoluminescence of KMgF3:LaF3 compounds have been found by deconvolving the glow curve with the General One Trap model (GOT). For the fitting procedure the Levenberg-Marquardt method has been employed. Tm-T(stop) measurements along with initial rise measurements were performed in order to estimate the number of peaks the glow curve is made up of, and the corresponding activation energies. Instead of the Runge-Kutta method, a novel algorithm has been employed to integrate the differential equation of the GOT model, which reduces the computational time nearly 30 times with respect to the former when the glow curve is recorded with a lineal heating rate profile. The strong computational time reduction makes feasible a large number of runs with different guess values. An interesting result is that the concentration of disconnected deep traps is much less than the concentration of trap centres.

Comparison of the energy-response factor of LiF and Al2O3 in radiotherapy beams.

A Monte Carlo study of the energy-response factor of aluminium oxide (Al2O3) and lithium fluoride (LiF) TLDs in kilovoltage and megavoltage photon beams relative to 60Co gamma rays has been performed using EGSnrc Monte Carlo simulations. The sensitive volume of the detector was simulated as a disc of diameter 2.85 mm and thickness 1 mm. The phantom material was water and the irradiation depth was 2.0 cm in kilovoltage photon beams and 5.0 cm for megavoltage photon beams. The results show that the energy-response of the Al2O3 and LiF-TLDs is constant within 3% for photon beam energies in the energy range of 60Co gamma rays to 25 MV X rays. However, both detectors show an enhanced response for kilovoltage photon beams, which in the case of 50 kV X rays is 3.2 times higher than that for 60Co gamma rays. The energy-response factor was 1.46 for LiF irradiated in 50 kV X rays. The Al2O3 detector has an energy-response that is 2.2 times higher than that of LiF in 50 kV X rays decreasing to 1.19 for 250 kV X rays. The results show that the addition of 0.1 or 1% of carbon by weight (as dopant) into the Al2O3 does not change the Monte Carlo determined energy-response factor by more than 1%.

Low temperature radioluminescence of LiF:Mg,Cu,P.

Low temperature radioluminescence spectra of LiF, variously co-doped with Mg, Cu and P, show highly unusual temperature dependencies which resemble thermoluminescence data. The signals include intense peaks and a relatively weak continuous background. One peak occurs below 30 K, together with a major peak near 125 K. The signals are highly sensitive to the dopants and slightly sensitive to X-ray dose rate. The role of donor acceptor pairs and the perturbations from intrinsic defects formed by ionisation can be used to describe all the observations. The 290 nm emission band is linked to H center annealing.

Comparative study of LiF:Mg,Cu,Na,Si and Li2B4O7:Cu,Ag,P TL detectors.

Recently, two new types of 'tissue equivalent' thermoluminescent detectors (TLDs) have aroused attention: LiF:Mg,Cu,Na,Si and Li2B4O7:Cu,Ag,P. In this work the characteristics of both detectors were compared with the characteristics of the well-known type LiF:Mg,Ti detector, TLD-100. The following properties were investigated: the glow curve structures, relative sensitivity, batch homogeneity and uniformity, detection threshold, reproducibility of the response, linearity in the wide dose range and fading. Also, the energy dependence for medium and low energy X rays was determined in the range of mean energies between 33 and 116 keV. The results confirmed 'tissue equivalency' of both new types in the investigated range of photon energies. LiF:Mg,Cu,Na,Si detector has very high sensitivity (approximately 75 times higher than that of TLD-100) and is convenient for use in a very low range of doses. Li2B4O7:Cu,Ag,P detector shows some improvements in comparison with the previously prepared types of lithium borate. The most important is the five times higher sensitivity than that of TLD-100. This detector is also very promising, especially in medical dosimetry.

Comparison of two extremity dosemeters based on LiF:Mg,Cu,P thin detectors for mixed beta-gamma fields.

Two types of thin LiF:Mg,Cu,P detectors, GR-200F and MCP-Ns, have been characterised for use in the design of an extremity dosemeter for mixed beta-photon radiation fields. Both detectors consist of an extremely thin layer of sensitive material with effective thicknesses of 5 and 8 mg cm(-2), respectively, held in a 5 mg cm(-2) PVC ring holder. Dosimetric performance was analysed according to the ISO 12794 standard and compared with 240 mg cm(-2) TLD-100 measurements. In particular, the energy response was obtained for ISO narrow X-ray spectra, (137)Cs, (60)Co, (204)Tl and (90)Sr/(90)Y. From these measurements a mean calibration factor was calculated to estimate H(p)(0.07). Subsequently, the performance of the dosemeters was checked for a set of 10 different mixed photon and beta-photon fields. The study shows that the proposed dosemeters can estimate H(p)(0.07) in a wide range of mixed beta-photon fields with a maximum deviation from the given dose of 30% and an overall uncertainty of the order of 25% (k = 1). However, the results also highlight a large variability among the different thin detectors and, thus, the standard TLD-100 material is recommended whenever the workplace does not include low-energy beta radiation.

Time-resolved spectroscopy of LiF:Mg,Cu,P.

Time-resolved spectroscopy measurements of LiF:Mg,Cu,P luminescence are presented to obtain a better understanding of the emission characteristics of this material. The intensities and decay of the emission bands were studied as a function of annealing temperature and ionising radiation (gamma) dose. Two peaks in the emission were observed at 367 and 466 nm when excited by the 266 nm laser radiation. The luminescence spectrum under band-to-band X-ray excitation shows a dominant emission approximately 390-400 nm, which resembles the reported thermoluminescence emission and is clearly different from the spectrum obtained using the 266 nm pulsed laser excitation. Annealing of the material to 300 degrees C increases the intensity of the 367 and 466 nm emission bands by an order of magnitude as well as changes the relative intensity of the bands. Additional emission bands, which are not evident in the thermoluminescence emission spectra, are seen at longer wavelengths that also increase with dose. Possible explanations for the observed emission spectra are discussed in this paper.