Structural, Spectroscopic, and Theoretical Investigation of a T-Shaped [Fe3(µ3-O)] Cluster.

The synthesis, X-ray crystal and electronic structures of [Fe3(µ3-O)(mpmae)2(OAc)2 Cl3], 1, where mpmae-H = 2-(N-methyl-N-((pyridine-2-yl)methyl)amino)ethanol, are described. This cluster comprises three high-spin ferric ions and exhibits a T-shaped site topology. Variable-frequency electron paramagnetic resonance measurements performed on single crystals of 1 demonstrate a total spin ST = 5/2 ground state, characterized by a small, negative, and nearly axial zero-field splitting tensor D = -0.49 cm-1, E/D ≈ 0.055. Analysis of magnetic susceptibility, magnetization, and magneto-structural correlations further corroborate the presence of a sextet ground-spin state. The observed ground state originates from the strong anti-ferromagnetic interaction of two iron(III) spins, with J = 115(5) cm-1, that, in turn, are only weakly coupled to the spin of the third site, with j = 7(1) cm-1. These exchange interactions lead to a ground state with magnetic properties that are essentially entirely determined by the weakly coupled site. The contributions of the individual spins to the total ground state of the cluster were monitored using variable-field 57Fe Mössbauer spectroscopy. Field-dependent spectra reveal that, while one of the iron sites exhibits a large negative internal field, typical of ferric ions, the other two sites exhibit small, but not null, negative and positive internal fields. A theoretical analysis reveals that these small internal fields originate from the mixing of the lowest ST = 5/2 excited state into the ground state which, in turn, is induced by a minute structural distortion.

[Photoinduced intra-molecular energy transfer of a novel phthalocyanine zinc(II) bearing poly (aryl benzyl ether) dendritic substitutents with carboxylic terminal].

The photoinduced intra-molecular energy transfer in phthalocyanine zinc(II) bearing poly (aryl benzyl ether) dendritic substituents with carboxylic terminal was studied by steady-state, time-resolved fluorescence and UV/Vis spectroscopic methods. The result shows that the complexes mainly existed as monomers in dimethyl sulfoxide. The light-harvesting ability of this series of dendritic phthalocyanines increased with the dendron generation under 270 nm. The effects of the dendron generation on the fluorescence characteristics of phthalocyanine cores was significantly, and the fluorescence lifetime and fluorescent quantum yield decreased with the increase of the dendron generation. Intra-molecular energy could be transferred from peripheral dendron acting as an energy hydrazine to the phthalocyanine core during a photo-induced process. With the dendrimer increasing, the intra-molecular energy transfer quantum yield increased. These results obviously indicated that this series of dendritic phthalocyanines is a king of novel compound with light-harvesting structure.

Asymmetric silicon phthalocyanine based nanoparticle with spatiotemporally targeting of mitochondria for synergistic apoptosis-ferroptosis antitumor treatment.

A promising therapeutic strategy in cancer treatment merges photodynamic therapy (PDT) induced apoptosis with ferroptosis, a form of programmed cell death governed by iron-dependent lipid peroxidation. Given the pivotal role of mitochondria in ferroptosis, the development of photosensitizers that specifically provoke mitochondrial dysfunction and consequentially trigger ferroptosis via PDT is of significant interest. To this end, we have designed and synthesized a novel nanoparticle, termed FECTPN, tailored to address this requisite. FECTPN harnesses a trifecta of critical attributes: precision mitochondria targeting, photoactivation capability, pH-responsive drug release, and synergistic apoptosis-ferroptosis antitumor treatment. This nanoparticle was formulated by conjugating an asymmetric silicon phthalocyanine, Chol-SiPc-TPP, with the ferroptosis inducer Erastin onto a ferritin. The Chol-SiPc-TPP is a chemically crafted entity featuring cholesteryl (Chol) and triphenylphosphine (TPP) functionalities bonded axially to the silicon phthalocyanine, enhancing mitochondrial affinity and leading to effective PDT and subsequent apoptosis of cells. Upon cellular uptake, FECTPN preferentially localizes to mitochondria, facilitated by Chol-SiPc-TPP's targeting mechanics. Photoactivation induces the synchronized release of Chol-SiPc-TPP and Erastin in the mitochondria's alkaline domain, driving the escalation of both ROSs and lipid peroxidation. These processes culminate in elevated antitumor activity compared to the singular application of Chol-SiPc-TPP-mediated PDT. A notable observation is the pronounced enhancement in glutathione peroxidase-4 (GPX4) expression within MCF-7 cells treated with FECTPN and subjected to light exposure, reflecting intensified oxidative stress. This study offers compelling evidence that FECTPN can effectively induce ferroptosis and reinforces the paradigm of a synergistic apoptosis-ferroptosis pathway in cancer therapy, proposing a novel route for augmented antitumor treatments.

Enhancing antitumor efficacy of NIR-I region zinc phthalocyanine@upconversion nanoparticle through lysosomal escape and mitochondria targeting.

Accurately visualizing the intracellular trafficking of upconversion nanoparticles (UCNPs) loaded with phthalocyanines and achieving precise photodynamic therapy (PDT) using near-infrared (NIR) laser irradiation still present challenges. In this study, a novel NIR laser-triggered upconversion luminescence (UCL) imaging-guided nanoparticle called FA@TPA-NH-ZnPc@UCNPs (FTU) was developed for PDT. FTU consisted of UCNPs, folic acid (FA), and triphenylamino-phenylaniline zinc phthalocyanine (TPA-NH-ZnPc). Notably, TPA-NH-ZnPc showcases aggregation-induced emission (AIE) characteristic and NIR absorption properties at 741 nm, synthesized initially via molybdenum-catalyzed condensation reaction. The UCL emitted by FTU enable real-time visualization of their subcellular localization and intracellular trafficking within ovarian cancer HO-8910 cells. Fluorescence images revealed that FTU managed to escape from lysosomes due to the "proton sponge" effect of TPA-NH-ZnPc. The FA ligands on the surface of FTU further directed their transport and accumulation within mitochondria. When excited by a 980 nm laser, FTU exhibited UCL and activated TPA-NH-ZnPc, consequently generating cytotoxic singlet oxygen (1O2), disrupted mitochondrial function and induced apoptosis in cancer cells, which demonstrated great potential for tumor ablation.

Fluorinated triphenylamine silicon phthalocyanine nanoparticles with two-color imaging guided in vitro photodynamic therapy through lysosomal dysfunction.

Lysosome-targeting therapy has emerged as a promising strategy for combating drug-resistant tumors. However, the synthesis of nanodrugs to achieve efficient lysosome targeting remains a challenging task. In this study, a nanoparticle DSPE@TPA-FBPA-SiPc was developed for lysosome targeting therapy. The nanoparticle was prepared by loading 2-[4-(diphenylamino)-1-diphenicacid-1-carbobenzoxy-4-(1,1,1,3,3,3-hexafluoropropane-4-phenoxy) silicon phthalocyanine (TPA-FBPA-SiPc) into 1,2-distearoyl-sn­glycero-3-phosphoethanolamine-N-[succinyl(polyethyleneglycol)-2000] (DSPE). DSPE@TPA-FBPA-SiPc demonstrated remarkable capabilities such as two-color imaging, lysosome targeting and in vitro photodynamic therapy functions. The results revealed that DSPE@TPA-FBPA-SiPc efficiently accumulated in lysosomes, leading to generation of a high amount of reactive oxygen species upon irradiation. This induced apoptosis in MCF-7 cells by disrupting lysosomal function. Consequently, DSPE@TPA-FBPA-SiPc holds great potential as a photosensitizer for photodynamic therapy, utilizing the lysosomal-mediated cell death pathway.

Chlorophenyl thiophene silicon phthalocyanine: Synthesis, two-photon bioimaging-guided lysosome target, and in vitro photodynamic efficacy.

The development of efficient photosensitizers with high singlet oxygen quantum yield, strong fluorescent emission, excellent photostability, and specific organelle targeting is in great demand for the enhancement of PDT treatment efficiency. This study designed and synthesized a new two-photon photosensitizer chlorophenyl thiophene axially substituted silicon (IV) phthalocyanine (CBT-SiPc). CBT-SiPc showed specific targeting of lysosomes in living cells and good biocompatibility. Furthermore, high 1O2 generation efficiency and high PDT efficiency in MCF-7 breast cancers under irradiation were also demonstrated. The novel CBT-SiPc showed great potential in the application of lysosome-targeted and two-photon bioimaging-guided photodynamic cancer therapy.

A piperazine-substituted phthalocyanine with rapid cellular uptake and dual organelle-targeting for in vitro photodynamic therapy.

The rational design of photosensitizers with rapid cellular uptake and dual-organelle targeting ability is essential for enhancing the efficacy of photodynamic therapy (PDT). However, achieving this goal is a great challenge. In this paper, a novel axial piperazine substituted (PIP) silicon phthalocyanine (PIP-SiPc) has been synthesized. The PIP substitution significantly improved the cellular uptake of PIP-SiPc in MCF-7 breast cancer cells, as demonstrated by two-photon fluorescence imaging combined with fluorescence correlation spectroscopy. Additionally, PIP-SiPc was able to target both mitochondria and lysosomes simultaneously. Notably, PIP-SiPc exhibited remarkable singlet oxygen generation ability, leading to apoptosis in cancer cells upon irradiation, with an IC50 value of only 0.2 µM. These findings highlight the effectiveness of PIP-SiPc as a multifunctional photosensitizer for PDT.

Morpholinyl silicon phthalocyanine nanoparticles with lysosome cell death and two-photon imaging functions for in vitro photodynamic therapy of cancer cells.

The lysosome is an important target for realizing antitumor therapy. Lysosomal cell death exerts significant therapeutic effects on apoptosis and drug-resistance. The development of lysosome-targeting nanoparticles to obtain efficient cancer treatment is challenging. In this article, nanoparticles composed of DSPE@M-SiPc and possessing bright two-photon fluorescence, lysosome targeting ability, and photodynamic therapy multifunctionalities are prepared by encapsulating morpholinyl-substituted silicon phthalocyanine (M-SiPc) with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly(ethylene glycol))-2000] (DSPE). Two photon fluorescence bioimaging showed that M-SiPc and DSPE@M-SiPc mainly locate in lysosomes after cellular internalization. Upon irradiation, DSPE@M-SiPc effectively generates reactive oxygen species and damages the function of lysosome, subsequently leading to lysosomal cell death. DSPE@M-SiPc is a promising photosensitizer for cancer treatment.

CdSe/ZnS core shell quantum dot-based FRET binary oligonucleotide probes for detection of nucleic acids.

We report the design, synthesis, and characterization of a binary oligonucleotideprobe for selective DNA or RNA detection. The probe is based on fluorescence resonance energy transfer (FRET) from quantum dot (CdSe/ZnS core shell) DNA conjugates to organic dye (cyanine-5) DNA conjugates. Selective hybridization of the donor/acceptor DNA conjugates to target DNA enhances FRET and a change in fluorescence signature was observed.

Bromopropylate Imidazoliumyl Substituted Silicon Phthalocyanine for Mitochondria-Targeting, Two-Photon Imaging Guided in Vitro Photodynamic Therapy.

Maximization of phototoxic damage on tumor is essential for effective anticancer photodynamic therapy (PDT). Highly cancer-cell-organelle-specific delivery of efficient photosensitizers (PSs) in vitro and in vivo is in great demand. In this paper, a novel water-soluble mitochondria targeted cationic bromopropylate imidazoliumyl axially substituted silicon (IV) phthalocyanine (Br-ID-SiPc) is developed to improve PDT efficiency by enhancing the subcellular localization of photosensitizers. Benefiting from the targeting capability of bromopropylate imidazoliumyl, Br-ID-SiPc can selectively accumulate in mitochondria after cellular uptake, this process could be tracked by two-photon imaging. Br-ID-SiPc effectively damaged the circular plasmid DNA of mitochondria and induced HO-8910 cells apoptosis. Our results indicate that Br-ID-SiPc is a potential photosensitizer which can be used as a mitochondria-targeting and two-photon fluorescent imaging molecule for PDT of cancers.

Accuracy Improvement Method Based on Characteristic Database Classification for IMRT Dose Prediction in Cervical Cancer: Scientifically Training Data Selection.

Purpose: Consistent training and testing datasets can lead to good performance for deep learning (DL) models. However, a large high-quality training dataset for unusual clinical scenarios is usually not easy to collect. The work aims to find optimal training data collection strategies for DL-based dose prediction models. Materials and Methods: A total of 325 clinically approved cervical IMRT plans were utilized. We designed comparison experiments to investigate the impact of (1) beam angles, (2) the number of beams, and (3) patient position for DL dose prediction models. In addition, a novel geometry-based beam mask generation method was proposed to provide beam setting information in the model training process. What is more, we proposed a new training strategy named "full-database pre-trained strategy". Results: The model trained with a homogeneous dataset with the same beam settings achieved the best performance [mean prediction errors of planning target volume (PTV), bladder, and rectum: 0.29 ± 0.15%, 3.1 ± 2.55%, and 3.15 ± 1.69%] compared with that trained with large mixed beam setting plans (mean errors of PTV, bladder, and rectum: 0.8 ± 0.14%, 5.03 ± 2.2%, and 4.45 ± 1.4%). A homogeneous dataset is more accessible to train an accurate dose prediction model (mean errors of PTV, bladder and rectum: 2.2 ± 0.15%, 5 ± 2.1%, and 3.23 ± 1.53%) than a non-homogeneous one (mean errors of PTV, bladder and rectum: 2.55 ± 0.12%, 6.33 ± 2.46%, and 4.76 ± 2.91%) without other processing approaches. The added beam mask can constantly improve the model performance, especially for datasets with different beam settings (mean errors of PTV, bladder, and rectum improved from 0.8 ± 0.14%, 5.03 ± 2.2%, and 4.45 ± 1.4% to 0.29 ± 0.15%, 3.1 ± 2.55%, and 3.15 ± 1.69%). Conclusions: A consistent dataset is recommended to form a patient-specific IMRT dose prediction model. When a consistent dataset is not accessible to collect, a large dataset with different beam angles and a training model with beam information can also get a relatively good model. The full-database pre-trained strategies can rapidly form an accuracy model from a pre-trained model. The proposed beam mask can effectively improve the model performance. Our study may be helpful for further dose prediction studies in terms of training strategies or database establishment.

Microbacterium kunmingensis sp. nov., an attached bacterium of Microcystis aeruginosa.

A Gram-stain positive, aerobic, rod-shaped actinobacterial strain designated as JXJ CY 27-2T was isolated from the culture of Microcystis aeruginosa FACHB-905 (Maf) collected from Lake Kunming, southwest China. The isolate was catalase positive, oxidase negative, and able to grow at 10.0-44.0 °C, pH 5.0-10.0 and 0-5.0% NaCl. Based on the 16S rRNA gene sequences, JXJ CY 27-2T showed high similarities of 98.54-98.55% with Microbacterium invictum DSM 19600T, Microbacterium saccharophilum DSM 28107T, and Microbacterium aoyamense DSM 19461T, and less than 98.47% similarities with other members of the genus. Its major cellular fatty acids were anteiso-C17:0 and anteiso-C15:0. The predominant menaquinones were MK-11 and MK-12. The diagnostic diamino acid in the cell wall peptidoglycan was lysine. Whole cell sugars contained mannose, ribose, galactose, rhamnose and arabinose. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, two unidentified glycolipids, and an unidentified lipid. The DNA G + C content was 69.8%. The digital DNA-DNA hybridization and average nucleotide identity values between strain JXJ CY 27-2T and its three closest similar strains were 18.4-20.3% and 74.9-75.7%, respectively. Based on the above data, strain JXJ CY 27-2T was identified as a new species of the genus Microbacterium, for which the name Microbacterium kunmingensis sp. nov. is proposed. The type strain is JXJ CY 27-2T (=CGMCC 1.17506T = KCTC 49382T). Strain JXJ CY 27-2T could promote the growth of Maf by providing it with available phosphorus, nitrogen and probably other nutrients such as vitamins and indole-3-acetate.

In vitro photodynamic therapy on human U251 glioma cells with a novel photosensitiser ZnPcS4-BSA.

This article reports the phototoxicity effects of a novel photosensitiser ZnPcS4-BSA on human U251 glioma cells in vitro. The cellular uptake of ZnPcS4-BSA by U251 glioma cells was quantified by UV-spectra, and the optimal incubation time was determined. Human U251 glioma cells were incubated in ZnPcS4-BSA of various concentrations, and received laser irradiation of different energy densities. Cell survival rates were measured by CCK-8 assay. Flow cytometer was used to detect apoptosis. Expression of vascular endothelial growth factor (VEGF) gene was detected by real-time PCR in U251 cells after photodynamic therapy (PDT), and ß-actin was used as an internal standard. The normal U251 cells severed as controls. Results indicate that the uptake of ZnPcS4-BSA by U251 glioma cells reaches maximum after incubation for 4 hours. ZnPcS4-BSA with different concentrations without light irradiation has no significant effects on cell survival rates. Without ZnPcS4-BSA incubation, cell survival rate of high-dose group (400 J/cm(2)) is the lowest, whereas no significant difference has been found between any other two groups. At laser irradiation of 150 J/cm(2), inhibition rates of the cells increase with ZnPcS4-BSA concentration, and half-inhibitory concentration (IC50) is 0.16 µmol/L. Apoptosis rate of the cells after PDT is significantly higher than that of the control group (p < 0.01). The VEGF expression in the cells increases 5.616 times after PDT. The novel ZnPcS4-BSA is a good photosensitiser for PDT towards U251 glioma cells. The ZnPcS4-BSA based PDT can induce effective apoptosis.

Visualization photofragmentation-induced rhodamine B release from gold nanorod delivery system by combination two-photon luminescence imaging with correlation spectroscopy.

Plasmon-enhanced gold nanorod (AuNR) with high photothermal conversion efficiency is a promising light-controllable nanodrug delivery system for cancer therapy. Understanding the mechanism for the light-controllable drug release of AuNR delivery systems is important for the development of nanomedicine. In this study, the rhodamine B (RB) released from AuNR-RB nanodelivery system was quantitated and visualized by using two-photon luminescence (TPL) imaging combined with correlation spectroscopy. The photofragmentation of AuNR induced by femtosecond pulsed laser was revealed by TPL correlation spectroscopy when the laser energy was above the thermal damage threshold of AuNR, and the RB released from this nanodrug delivery system was visualized by TPL imaging. Furthermore, the photofragmentation-induced release of RB from AuNR-RB nanodelivery system was visualized in living MCF-7 breast cancer cells by TPL imaging combined with correlation spectroscopy. These results provided a novel optical approach to quantify the release of drugs from gold nanocarriers in complex biological media.

Distribution, Trafficking, and in Vitro Photodynamic Therapy Efficacy of Cholesterol Silicon(IV) Phthalocyanine and Its Nanoparticles in Breast Cancer Cells.

A cholesterol silicon(IV) phthalocyanine (Chol-Pc) and a water-soluble Chol-Pc based nanoparticle (DSPE@Chol-Pc), which was prepared using 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly(ethylene glycol))-2000] (DSPE-PEG2000) as a nanocarrier were developed. Chol-Pc readily distributed within the cholesterol-rich domains and was preferentially localized in the Golgi apparatus after being transported into the cells. The trafficking of DSPE@Chol-Pc in breast cancer cells was visualized by tracking the fluorescence of Chol-Pc and FITC-labeled DSPE-PEG2000 through two-photonic imaging in real-time. It was discovered that Chol-Pc disassociated from the DSPE-PEG2000 on the plasma membrane and traveled to the cholesterol-rich domains soon afterward. Both DSPE@Chol-Pc and Chol-Pc effectively mediated photodynamic therapy to kill the breast cancer cells. After light irradiation, we found that the organizations of clustered cholesterol-rich domains in cells were destroyed, presumably leading to the death of cells for photodynamic therapy. It should be noted that DSPE@Chol-Pc is highly soluble in aqueous solution and has strong red fluorescence under two-photon excitation. Thus, it could be an excellent probe for detecting cholesterol-rich domains and studying transport processes of cholesterol in living cells.

[Study on the interaction of tetra-sulfonated phathalocyanine cobalt with bovine serum albumin].

The tetra-sulfonated phathalocyanine cobalt(CoPcS4)was synthesized by using 4-sulfonic phthalic acid as raw material, CoCl2 as template agent and (NH4)2 MoO4 as catalyst. CoPcS4 was demonstrated to be C4h mono-isomer by elementary analysis, IR, NMR and HLPC. Depolymerization of CoPcS4 was found in DMSO. The depolymerization increased with the pH value raising. The interaction of tetra-sulfonated phathalocyanine cobalt with bovine serum albumin (BSA) was studied by UV-Vis and fluorescence spectra The number of binding sites and binding constant were determined at equal pace of the order of magnitude 10(5) L x mol(-1). CoPcS4 binds with BSA at Site I and Site II. In conclusion, COPcS4 binds with BSA commendably and albumin plays a role of storage and transport.

Morpholinyl dendrimer phthalocyanine: synthesis, photophysical properties and photoinduced intramolecular electron transfer.

In this work, a novel series of morpholinyl dendrimer phthalocyanines were synthesized. Their structures were characterized by 1H NMR, IR, elemental analysis, ESI-MS as well as MALDI-TOF MS. The photophysical properties of these phthalocyanines were studied by UV/Vis and fluorescence spectroscopic methods. The photophysical properties of these dendrimer phthalocyanines exhibited dependence on the number of morpholinyl groups and the central ion. The photoinduced intramolecular electron transfer from the morpholinyl groups to the phthalocyanine ring was evidenced by the remarkably quenched fluorescence intensity and shortened lifetime of the silicon phthalocyanine. This difference in photoinduced intramolecular electron transfer effect for axially and peripherally substituted morpholinyl dendrimer phthalocyanines was also studied. Besides, introduction of morpholinyl groups on the dendrimer structure could enhance water solubility as well as increase the singlet oxygen quantum yield.

A polyfluoroalkyl substituted phthalocyanine based supramolecular light switch for photothermal and photodynamic antibacterial activity against Escherichia coli.

A polyfluoroalkyl substituted phthalocyanine based supramolecular light switch was assembled by the host-guest interaction between the novel polyfluoroalkyl substituted silicon phthalocyanine and pyrene-ß-cyclodextrin, which was attached on the sidewalls of SWNTs through the pyrene groups. This supermolecule can not only absorb light to convert its energy into heat energy, but also respond to light, control the release of phthalocyanine and restore fluorescence and produce singlet oxygen for a synergistic photothermal and photodynamic effect against Escherichia coli.

Zinc phthalocyanine tetrasulfonate (ZnPcS4): a new photosensitizer for photodynamic therapy in choroidal neovascularization.

PURPOSE: The aim of this sutdy was to demonstrate the selective localization of a new photosensitizer, zinc phthalocyanine tetrasulfonate (ZnPcS(4)), in rat eyes and investigate the ability of ZnPcS(4) to produce a photochemical closure of experimental choroidal neovascularization (CNV) upon irradiation with a 670-nm laser light. METHODS: To determine the biodistribution of ZnPcS(4) and the optimal timing of laser irradiation after photosensitizer administration, fluorescence microscopy with ZnPcS(4) was performed. CNV was created in the fundi of Brown-Norway rats using the argon laser model and documented by fluorescein angiography (FFA) and optical coherence tomography (OCT). Photodynamic therapy (PDT) was performed at the dose of 2.0 mg/m(2) and laser fluences of 600 mW/cm(2) on the CNV and on normal retina and choroid. Treatment outcomes were assessed by FFA and OCT and confirmed by light and electron microscopy. RESULTS: Fluorescence microscopy demonstrated intense ZnPcS(4) fluorescence from the CNV, choriocapillaris, and retinal pigment epithelial cells. Peak ZnPcS(4) intensities in the choriocapillaris and CNV were detected at 10-20 min after an intravenous injection. FFA and OCT indicated that irradiation with 670 nm of laser light 20 min after a ZnPcS(4) injection produced a complete closure of CNV with minimal damage to the overlying retina. Histologic studies, using light and electron microscopy, demonstrated CNV endothelial cell necrosis with minimal damage to the surrounding tissues. CONCLUSIONS: ZnPcS(4) selectively localizes to the choriocapillaris and CNV in rats, resulting in the occlusion of laser-induced CNV with minimal damage to the retina tissues. ZnPcS(4) -PDT is a potential new strategy for the treatment of macular degeneration and other human diseases manifesting as CNV.