Deoxyglucose-conjugated persistent luminescent nanoparticles for theragnostic application in fibrosarcoma tumor model.

Deoxyglucose conjugated nanoparticles with persistent luminescence have shown theragnostic potential. In this study, deoxyglucose-conjugated nano-particles with persistent luminescence properties were synthesized, and their theragnostic potential was evaluated in fibrosarcoma cancer cells and a tumor model. The uptake of nano-formulation was found to be higher in mouse fibrosarcoma (WEHI-164) cells cultured in a medium without glucose. Nanoparticles showed a higher killing ability for cancer cells compared to normal cells. A significant accumulation of nanoparticles to the tumor site in mice was evident by the increased tumor/normal leg ratio, resulting in a significant decrease in tumor volume and weight. Histopathological studies showed a significant decrease in the number of dividing mitotic cells but a greater number of apoptotic/necrotic cells in nanoparticle-treated tumor tissues, which was correlated with a lower magnitude of Ki-67 expression (a proliferation marker). Consequently, our results showed the potential of our nano-formulation for cancer theragnosis.

Mesoporous Silica-Coated Upconversion Nanoparticles Assisted Photodynamic Therapy Using 5-Aminolevulinic Acid: Mechanistic and In Vivo Studies.

Exclusively red-emitting upconversion nanoparticles (UCNPs) with the composition NaErF4:0.5%Tm as a core and NaYF4 as a shell were synthesized for performing photodynamic therapy (PDT). A possible mechanism was proposed for core-shell UCNPs formation. For loading a maximum amount of 5-aminolevulinic acid (5-ALA), mesoporous silica coating was performed on UCNPs. Studies under dark conditions confirmed the biocompatibility of 5-ALA-loaded UCNPs formulation (UCNPs-5-ALA) with MCF-7 cells. Meanwhile, studies under light-exposed conditions exhibited effective cytotoxicity against MCF-7 cells. Studies employing D2O-based cell cultured media and addition of DABCO in cell culture established that the cell death was due to oxidation of cellular components by reactive oxygen species (ROS) triggering the apoptosis. The formation of ROS was confirmed by DCF(H)DA-based ROS analysis via fluorescence microscopy to demonstrate the ROS production, which mediates the programmed cell death. Additionally, we have validated the apoptosis in MCF-7 cells with flow cytometry analyses. This was further confirmed by an electrophoretic mobility shift assay on nuclear extract and measurement of mitochondrial membrane potential. In the case of animal model studies, the formulation UCNPs-5-ALA without irradiation (980 nm) did not possess any in vivo cytotoxicity on tumor-induced SCID mice and there was a minimum migration of UCNPs-5-ALA to the vital organs but maximum retention at the tumor site only. Meanwhile, only the mice treated with UCNPs-5-ALA and irradiated on the tumor region with 980 nm laser (500 mW) for 20 min possessed a tumor with a size reduced to about 75% as compared with the corresponding control groups. To the best of our knowledge, this type of study was conducted for the first time employing exclusively red-emitting phosphors for effective PDT.

Facile Synthesis of a Pt(IV) Prodrug of Cisplatin and Its Intrinsically 195mPt Labeled Analog: A Step Closer to Cancer Theranostic.

BACKGROUND AIMS AND OBJECTIVES: Cisplatin is extensively used in chemotherapy for treatment of a broad range of cancers. But its undesired side reactions with biomolecules that lead to severe side effects especially on kidney and nervous system, are limiting its clinical utility. To reduce its side effects, the kinetically inert Pt(IV) prodrug was recognized as an alternative approach from satisfactory results of preliminary experiments. But, its approval as anticancer drug for clinical use requires detailed investigations of its anticancer action and pharmacological pathways by employing its analogue which can be traced by a suitable technique. As a step closer towards translation of Pt(IV)-based prodrug from research to clinical level, a protocol for efficient synthesis of 195mPt-radiolabeled Pt(IV) prodrug was devised. MATERIALS AND METHODS: In order to achieve the aim, we started synthesis from elemental platinum avoiding lengthy steps. The synthesis protocol was standardized on its cold analogue, as [PtCl2(NH3)2(OCOCH2CH2COOH)2] which has been characterized with nuclear magnetic resonance (1H, 13C{1H} and 195Pt{1H}) spectroscopy, microanalyses and cyclic voltammetry. Also, cytotoxicity of [PtCl2(OCOCH2CH2COOH)2(NH3)2] was evaluated against MCF-7 human breast cancer cell lines using cisplatin as test control. RESULTS: Intrinsically, 195mPt-labeled analogue of prodrug was obtained with high radionuclidic and radiochemical purity. It was confirmed by chromatography and γ-ray spectrometry. CONCLUSION: The 195mPt-radiolabeled prodrug was synthesized in a facile manner. It can be utilized in evaluating the mechanism of anticancer action and pharmacokinetics by enabling synergistic use of molecular imaging and targeted drug delivery.

Generation of Multiply Charged Argon Ions in Nanosecond Laser Field Ionization of Argon Clusters.

Zhang and co-workers ( J. Phys. Chem. Lett. 2020, 11, 1100-1105) have recently reported results of experiments involving irradiation of argon clusters doped with bromofluorene chromophores by nanosecond-long pulses of 532 nm laser light. Multiply charged ions of atomic argon (Arn+, 1 ≤ n ≤ 7) and carbon (Cn+, 1 ≤ n ≤ 4) are observed, which are sought to be rationalized using an evaporation model. The distinguishing facet of exploding clusters being progenitors of energetic ions and electrons constitutes the key driver for contemporary research in laser-cluster interactions; it is, therefore, important to point out inconsistencies that are intrinsic to the model of Zhang and co-workers. In light of similar reports already in the literature, we show that their model is of limited utility in describing the dynamics that govern how fast, multiply charged atomic ions result from laser irradiation of gas-phase clusters. We posit that it is plasma behavior that underpins cluster heating and cluster explosion dynamics.

(TMT)n clusters as dilute debris-free tin source for generation of multiply charged tin ions-of relevance in extreme ultraviolet (EUV) lithography, under intense laser irradiation.

RATIONALE: Multiply charged tin ions ([Sn]8+ to [Sn]13+ ) are considered as ideal-emitters at extreme ultraviolet (EUV) wavelength ~ 13.5 nm, pertinent to advanced micro-electronic device fabrication. Solid tin targets have been widely explored for the generation of these ions, but debris generation has restricted their utilization. Tin-containing molecular clusters have, however, the potential to act as dilute and debris-free sources for the generation of tin ions, as investigated in the present study. METHODS: Efficient coupling of laser energy with clusters has been utilized for the generation of multiply charged tin ions. The ions generated have been characterized using time-of-flight mass spectrometry. By varying experimental parameters, the yield of multiply charged tin ions has been manipulated, for tetramethyltin (TMT) clusters. In addition, the energetic electrons and photons liberated upon laser-cluster interaction have been probed utilizing an in-house developed retarding field analyser. RESULTS: Interaction of tetramethyltin clusters with 1064 nm picosecond laser pulses of intensity ~ 1013 W/cm2 leads to the generation of multiply charged tin ions (up to [Sn]14+ ) and carbon ions (up to [C]4+ ). Efficient laser-cluster interaction is evident from the generation of multiply charged tin ions with ionization energy ~ 282 eV ([Sn]14+ ). By varying the experimental conditions, the distribution of multiply charged tin ions can be influenced to obtain significant relative ion yield of multiply charged tin ions from [Sn]8+ to [Sn]13+ . CONCLUSIONS: Tetramethyltin clusters have the potential to act as dilute and debris-free source for EUV lithographic applications, in contrast to bulk tin targets. The inherent properties of clusters, such as higher local density and the pulsed nature of the cluster source, are appropriate for EUV lithographic applications.

Tailoring Ion Charge State Distribution in Tetramethyltin Clusters under Influence of Moderate Intensity Picosecond Laser Pulse: Role of Laser Wavelength and Rate of Energy Deposition.

Systematic manipulation of ionic-outcome in laser-cluster interaction process has been realized for studies carried out on tetramethyltin (TMT) clusters under picosecond laser conditions, determined by choice of laser wavelength and intensity. As a function of laser intensity, TMT clusters exhibit gradual enhancement in overall ionization of its cluster constituents, up to a saturation level of ionization, which was distinct for different wavelengths (266, 355, and 532 nm). Simultaneously, systematic appearance of higher multiply charged atomic ions and shift in relative abundance of multiply charged atomic ions towards higher charge state was observed, using time-of-flight mass spectrometer. At saturation level, multiply charged atomic ions up to (C2+, Sn2+) at 266 nm, (C4+, Sn4+) at 355 nm, and (C4+, Sn6+) at 532 nm were detected. In addition, at 355 nm intra-cluster ion chemistry within the ionized cluster leads to generation of molecular hydrogen ion (H2+) and triatomic molecular hydrogen ion (H3+). Generation of multiply charged atomic ions is ascribed to efficient coupling of laser pulse with the cluster media, facilitated by inner-ionized electrons produced within the cluster, at the leading edge of laser pulse. Role of inner-ionized electrons is authenticated by measuring kinetic energy distribution of electrons liberated upon disintegration of excessively ionized cluster, under the influence of picosecond laser pulse. Graphical Abstract ᅟ.

Efficient coupling of nanosecond laser pulses with the cluster medium: Generation of hydrogen-like [C](5+) atomic ions.

RATIONALE: Clusters exhibit diverse photochemical behavior as a function of laser parameters, i.e. wavelength, pulse duration and intensity. One such aspect of cluster photochemistry is the generation of energetic multiply charged atomic ions, upon efficient interaction of clusters with intense laser pulses. In the present work, mass spectrometric investigations have been carried out on clusters of tetrahydrofuran (THF, C4 H8 O) - a saturated cyclic ether - subjected to nanosecond laser pulse (spanning from UV to IR wavelength range) with the aim of shedding light on the complex mechanism of laser-cluster interactions, which is still ambiguous. METHODS: THF clusters, generated via supersonic expansion of room-temperature THF vapours seeded in argon, were subjected to gigawatt intensity laser pulses (355, 532 and 1064 nm) obtained from a nanosecond Nd:YAG laser. The ions generated upon laser-cluster interaction were characterized using a time-of-flight mass spectrometer. RESULTS: At 355 nm, THF clusters exhibit the usual multiphoton dissociation/ionization behavior while, at 532 nm, observation of multiply charged atomic ions of carbon (up to [C](4+) ) and oxygen (up to [O](3+) ) was ascribed to Coulomb explosion of THF clusters. For studies carried out at 1064 nm, multiply charged atomic ions of carbon up to [C](5+) having an ionization energy of ~392 eV were observed, at a laser intensity of 10(10) W/cm(2) . CONCLUSIONS: The observation of [C](5+) atomic ions signifies efficient coupling of the laser energy with the cluster medium, using a nanosecond laser pulse. The results have been rationalized on the basis of a three-stage cluster ionization mechanism, suggesting the crucial role of the threshold laser intensity for initiating ionization within the cluster and generation of optimum charge centers for efficient extraction of energy from the laser pulse.

Effect of cluster expansion on photoionization of iron pentacarbonyl doped inert gas clusters under gigawatt intensity laser irradiation.

RATIONALE: The aim of the investigation was to understand the variation in ionization dynamics of inert gas clusters upon doping with species with lower ionization energy than the inert gas constituent. It was postulated that the use of dopant species having lower ionization energy would lead to facile ionization of doped inert gas clusters, resulting in enhancement of the charge state of atomic ions compared with those obtained for pure inert gas clusters. METHODS: Inert gas clusters (Ar(n), Kr(n) or Xe(n)) doped with iron pentacarbonyl were generated by supersonic expansion and subjected to gigawatt intensity laser pulses (266, 355, 532 and 1064 nm wavelengths) obtained from a nanosecond Nd:YAG laser. The ions generated upon laser-cluster interaction were characterized using a time-of-flight mass spectrometer. RESULTS: Upon interaction of the laser with the doped inert gas clusters, the charge states of the atomic ions were found to increase with the laser wavelength. However, the highest observed charge states were found to be lower for doped inert gas clusters than for pure inert gas clusters, at all laser wavelengths. CONCLUSIONS: Wavelength-dependent generation of multiply charged atomic ions has been explained based on the three stage model, i.e. multiphoton ionization ignited-inverse bremsstrahlung heating, and electron ionization. This model explains enhancement in the charge state of atomic ions with increasing wavelength based on inverse bremsstrahlung heating of the inner ionized electron, which is a more efficient process at longer wavelengths. Inefficient coupling of laser energy in the case of doped inert gas clusters compared with pure inert gas clusters has been rationalized on the basis of accelerated disintegration of the cluster due to facile initial ionization of dopant molecules having low ionization energy. The results suggest that a longer laser wavelength and a slower rate of cluster expansion facilitate the efficient transfer of optical energy into cluster systems.

Defect stabilization in ZnO nanorods by Mg2+ doping.

Luminescent ZnO and Zn0.95Mg0.05O nanorods with length around 0.5 to 3 microm and diameter 100-150 nm were prepared by a facile solvothermal method. On hydriding at room temperature, a change of morphology from nanorods with aspect ratio 5-10 to particles of sizes 100 nm has been observed in both ZnO and Zn0.95Mg0.05O. While hydrided Zn0.95Mg0.05O showed an enhanced defect related green emission, the same got suppressed in hydrided ZnO. Even though it is observed that zinc vacancies are present in both as prepared ZnO and Zn0.95Mg0.05O, luminescence studies indicate that zinc vacancies get stabilized in Zn0.95Mg0.05O on hydrogenation.

Surface chemistry of surfactant AOT-stabilized SnO(2) nanoparticles and effect of temperature.

SnO(2).xH(2)O nanoparticles were prepared at room temperature by the microemulsion route. Sodium bis(2-ethylhexyl) sulfosuccinate (AOT) was used as a surfactant to stabilize the nanoparticles. These nanoparticles show green luminescence at 510nm, which has been assigned to oxygen vacancies. Infrared spectra of samples heated in the temperature range 500-900 degrees C show bond formation between SnO(2) nanoparticles and SO(4)(2-), which arises from oxidation of SO(3)(-) present in AOT. This was further supported by X-ray diffraction. Shape transformations of the particles from triangular to spherical and then to rectangular was observed as the heat-treatment temperature was increased, and this is related to the surface energy of particles. An enhancement in emission intensity of Eu(3+) was observed when Eu(3+) ions were doped into the SnO(2) nanoparticles due to significant energy transfer from SnO(2) (or Eu-O) to Eu(3+) through surface-mediated energy transfer as compared to direct excitation of Eu(3+) at 397nm. Interestingly, these nanoparticles are dispersible in water, and can be incorporated into polymer-based materials such as polyvinyl alcohol to give homogeneous films, giving rise to blue and red emissions.

Wavelength-dependent Coulomb explosion in carbon disulphide (CS2) clusters: generation of energetic multiply charged carbon and sulphur ions.

A gigawatt laser-induced Coulomb explosion has been observed in carbon disulphide (CS(2)) clusters generating energetic, multiply charged [C](m+) (m = 1-4) and [S](n+) (n = 1-6) atomic ions of carbon and sulphur. The Coulomb explosion shows wavelength dependence. Comparison of these results with our earlier work shows that the polarizability and dipole moment might help in energy absorption from the laser field but they are not mandatory conditions for this low-intensity Coulomb explosion. The results show that in a field of 10(9) W/cm(2), absorption of 266 and 355 nm laser radiation by CS(2) clusters leads to multiphoton dissociation/ionization whereas at 532 nm the whole cluster explodes generating multiply charged atomic ions.

Laser spectroscopic excitation function and reaction threshold studies of the H + DCl --> HCl + D gas-phase isotope exchange reaction.

The dynamics of the gas-phase hydrogen atom exchange reaction H + DCl --> HCl + D were studied using the pulsed laser photolysis/laser induced fluorescence "pump-and-probe" method. Laser photolysis of H2S at 222 nm was used to generate nonequilibrium distributions of translationally excited hydrogen atoms at high dilution in a flowing moderator gas (Ar)/reagent (DCl) mixture. H and D atoms were detected with sub-Doppler resolution via Lyman-alpha laser induced fluorescence spectroscopy, which allowed the measurement of the line shapes of the moderated H atom Doppler profiles as well as the concentration of the D atoms produced in the H + DCl --> HCl + D reaction. From the measured H atom Doppler profiles, the time evolution of the initially generated nascent nonequilibrium H atom speed distribution toward its room-temperature thermal equilibrium form was determined. In this way, the excitation function and the reaction threshold (E0 = 0.65 +/- 0.13 eV) for the H + DCl --> HCl + D reaction could be determined from the measured nonequilibrium D atom formation rates and single collision absolute reaction cross-section values of 0.12 +/- 0.04 A2 and 0.45 +/- 0.11 A2 measured at reagent collision energies of 1.0 and 1.4 eV, respectively.