Small molecular target-based multifunctional upconversion nanocomposites for targeted and in-depth photodynamic and chemo-anticancer therapy.

A novel multifunctional nano-system, ZnPc-UCNPs-PEG-G, was designed for targeted and in-depth photodynamic therapy. The nano-system was built via covalent conjugation, in which phthalocyanine zinc (ZnPc), Gefitinib (G), NaYF4: Yb, Er (UCNPs) and PEG derivatives were employed as the photosensitizer, target moiety, upconversion nanomaterial and linker unit, respectively. The photophysical/chemical properties, in-depth photodynamic activity, cancer cell specificity and anticancer activity of ZnPc-UCNPs-PEG-G were investigated. The as-prepared ZnPc-UCNPs-PEG-G exhibits excellent photosensitizing ability, generating reactive oxygen species (ROS) via effective energy transfer from UCNP to phthalocyanine zinc. In addition, the composite exhibits specific affinity to HepG2 cancer cells and high anticancer activity. To the best of our knowledge, this is the only example of a UCNP platform that is capable of molecular targeted and in-depth photodynamic and chemo-anticancer therapy via the introduction of a small molecular targeting drug moiety.

Silicon Phthalocyanines Axially Disubstituted with Erlotinib toward Small-Molecular-Target-Based Photodynamic Therapy.

Small-molecular-target-based photodynamic therapy-a promising targeted anticancer strategy-was developed by conjugating zinc(II) phthalocyanine with a small-molecular-target-based anticancer drug. To prevent self-aggregation and avoid problems of phthalocyanine isomerization, two silicon phthalocyanines di-substituted axially with erlotinib have been synthesized and fully characterized. These conjugates are present in monomeric form in various solvents as well as culture media. Cell-based experiments showed that these conjugates localize in lysosomes and mitochondria, while maintaining high photodynamic activities (IC50 values as low as 8 nm under a light dose of 1.5 J cm-2 ). With erlotinib as the targeting moiety, two conjugates were found to exhibit high specificity for EGFR-overexpressing cancer cells. Various poly(ethylene glycol) (PEG) linker lengths were shown to have an effect on the photophysical/photochemical properties and on in vitro phototoxicity.

A Molecular Combination of Zinc(II) Phthalocyanine and Tamoxifen Derivative for Dual Targeting Photodynamic Therapy and Hormone Therapy.

The combination of photodynamic therapy and other cancer treatment modalities is a promising strategy to enhance therapeutic efficacy and reduce side effects. In this study, a tamoxifen-zinc(II) phthalocyanine conjugate linked by a triethylene glycol chain has been synthesized and characterized. Having tamoxifen as the targeting moiety, the conjugate shows high specific affinity to MCF-7 breast cancer cells overexpressed estrogen receptors (ERs) and tumor tissues, therefore leading to a cytotoxic effect in the dark due to the cytostatic tamoxifen moiety, and a high photocytotoxicity due to the photosensitizing phthalocyanine unit against the MCF-7 cancer cells. The high photodynamic activity of the conjugate can be attributed to its high cellular uptake and efficiency in generating intracellular reactive oxygen species. Upon addition of exogenous 17ß-estradiol as an ER inhibitor, the cellular uptake and photocytotoxicity of the conjugate are reduced significantly. As shown by confocal microscopy, the conjugate is preferentially localized in the lysosomes of the MCF-7 cells.

Preparation and In Vitro Photodynamic Activity of Glucosylated Zinc(II) Phthalocyanines as Underlying Targeting Photosensitizers.

Two novel glucosylated zinc(ІІ) phthalocyanines 7a-7b, as well as the acetyl-protected counterparts 6a-6b, have been synthesized by the Cu(I)-catalyzed 1,3-dipolar cycloaddition between the propargylated phthalocyanine and azide-substituted glucoses. All of these phthalocyanines were characterized with various spectroscopic methods and studied for their photo-physical, photo-chemical, and photo-biological properties. With glucose as the targeting unit, phthalocyanines 7a-7b exhibit a specific affinity to MCF-7 breast cancer cells over human embryonic lung fibroblast (HELF) cells, showing higher cellular uptake. Upon illumination, both photosensitizers show high cytotoxicity with IC50 as low as 0.032 µM toward MCF-7 cells, which are attributed to their high cellular uptake and low aggregation tendency in the biological media, promoting the generation of intracellular reactive oxygen species (ROS). Confocal laser fluorescence microscopic studies have also revealed that they have high and selective affinities to the lysosomes, but not the mitochondria, of MCF-7 cells. The results show that these two glucosylated zinc(II) phthalocyanines are potential anticancer agents for targeting photodynamic therapy.

[Total Gaseous Mercury and Mercury Emission from Natural Surface at One Typical Agricultural Region in Three Gorges Reservoir].

In situ measurement of total gaseous mercury (TGM) and mercury exchange fluxes between soil with different utilization patterns and atmosphere was conducted at one typical agricultural region in Three Gorges Reservoir. The TGM concentration ranged from 2.67 to 75.5 ng·m-3 with the average of (6.26±8.11) ng·m-3, higher than the global background value. An obvious seasonal variation of TGM was observed, and the TGM values in spring and winter were significantly higher than those in summer and autumn. It was found that the mercury fluxes varied from different landscapes with the emission fluxes at three land use types following the trend:rainfed cropland >paddy field >forest land. Seasonal variations of mercury emission were obvious with highest fluxes in summer and lowest in winter, while the highest daily mercury emission fluxes appeared at midday. Mercury emission fluxes in our study region were mainly controlled by air and soil temperature, humidity, light and ultraviolet, and the air temperature and ultraviolet were regarded as the main factors. The influence of Hg level in soil on Hg emission was not obvious in the presence of environmental factors and agricultural activity.

Molecular-target-based anticancer photosensitizer: synthesis and in vitro photodynamic activity of erlotinib-zinc(II) phthalocyanine conjugates.

Targeted photodynamic therapy is a new promising therapeutic strategy to overcome growing problems in contemporary medicine, such as drug toxicity and drug resistance. A series of erlotinib-zinc(II) phthalocyanine conjugates were designed and synthesized. Compared with unsubstituted zinc(II) phthalocyanine, these conjugates can successfully target EGFR-overexpressing cancer cells owing to the presence of the small molecular-target-based anticancer agent erlotinib. All conjugates were found to be essentially non-cytotoxic in the absence of light (up to 50 µM), but upon illumination, they show significantly high photo-cytotoxicity toward HepG2 cells, with IC50 values as low as 9.61-91.77 nM under a rather low light dose (λ=670 nm, 1.5 J cm(-2) ). Structure-activity relationships for these conjugates were assessed by determining their photophysical/photochemical properties, cellular uptake, and in vitro photodynamic activities. The results show that these conjugates are highly promising antitumor agents for molecular-target-based photodynamic therapy.

Synthesis and in vitro anticancer activity of zinc(II) phthalocyanines conjugated with coumarin derivatives for dual photodynamic and chemotherapy.

The combination of photodynamic therapy and chemotherapy is a promising strategy to overcome growing problems in contemporary medicine, such as low therapeutic efficacy and drug resistance. Four zinc(II) phthalocyanine-coumarin conjugates were synthesized and characterized. In these complexes, zinc(II) phthalocyanine was used as the photosensitizing unit, and a coumarin derivative was selected as the cytostatic moiety; the two components were linked via a tri(ethylene glycol) chain. These conjugates exhibit high photocytotoxicity against HepG2 human hepatocarcinoma cells, with low IC50 values in the range of 0.014-0.044 µM. The high photodynamic activities of these conjugates are in accordance with their low aggregation tendency and high cellular uptake. One of these conjugates exhibits high photocytotoxicity and significantly higher chemocytotoxicity. The results clearly show that the two antitumor components in these conjugates work in a cooperative fashion. As shown by confocal microscopy, the conjugates can localize in the mitochondria and lysosomes, and one of the conjugates can also localize in the cell nuclei.

A novel strategy for targeting photodynamic therapy. Molecular combo of photodynamic agent zinc(II) phthalocyanine and small molecule target-based anticancer drug erlotinib.

In this study, two phthalocyanine-erlotinib conjugates linked by an oligoethylene glycol chain have been synthesised and fully characterised. Having erlotinib as the targeting moiety, the two conjugates exhibited high specific affinity to HepG2 cancer cells and tumour tissues, therefore leading to high photodynamic activity.

Synthesis and in vitro photodynamic activity of oligomeric ethylene glycol-quinoline substituted zinc(II) phthalocyanine derivatives.

A new series of zinc(II) phthalocyanine derivatives have been synthesized and characterized. These macrocycles exhibited a sharp absorption band in the red visible region in DMF, which indicated that they were dissolved well and almost did not aggregate in this solvent. Compared with the unsubstituted zinc(II) phthalocyanine, all these phthalocyanines have a red-shifted Q-band (at 678-699 vs 670 nm) and exhibit a relatively weaker fluorescence emission and a higher efficiency at generating singlet oxygen. The monosubstituted photosensitizers also exhibit high photocytotoxicity toward HepG2 human hepatocarcinoma cells with IC50 values as low as 0.02-0.05 µM (λ = 670 nm, 80 mW·cm(-2), 1.5 J·cm(-2)). The high photodynamic activities of these compounds are in accordance with their low aggregation tendency and high cellular uptake. Their structure-activity relationship was assessed by determining the photophysical properties, cellular uptake, and in vitro photodynamic activities of this series of compounds. As shown by confocal microscopy, monosubstituted phthalocyanines can target the mitochondria and lysosomes of the cells, and tetrasubstituted phthalocyanines tend to target the lysosomes of the cells.

In vitro and in vivo anticancer activity evaluation of ursolic acid derivatives.

Twenty-three ursolic acid (1) derivatives 2-24 (ten novel compounds 8-10, 14-17 and 22-24) modified at the C-3 and the C-28 positions were synthesized, and their structures were confirmed by IR, (1)H NMR, MS, and elemental analysis. The single crystals of compounds 15 and 17 were obtained. The cytotoxic activity of the derivatives was evaluated against HepG2, BGC-823, SH-SY5Y, HeLa and HELF cells by the MTT assay. The induction of apoptosis and affects on the cell cycle distribution with compound 14 were assessed by fluorescence microscopy, flow cytometry and the activity of caspase-3 in HepG2 cells. Compounds 14-17 had more significant antiproliferative ability against the four cancer cell lines and low cytotoxicity to human embryonic lung fibroblast cells (HELF). Compounds 11, 14-16, 21 and 23 were particularly active against HepG2 cell growth. Compound 14 was selected to investigate cell apoptosis and cell cycle distribution. Flow cytometric analysis and morphologic changes of the cell exhibited that treatment of HepG2 cells with compound 14 led to cell apoptosis accompanied by cell cycle arrest at the S phase in a dose-dependent manner. Furthermore, the activity of the caspase-3 enzyme was increased in the treated cells. In vivo studies using H22 xenografts in Kunming mice were conducted with compound 14 at doses of 50, 100 and 150 mg/kg body weight. The results revealed that the medium dosage group (100 mg/kg) showed significant anticancer activity (45.6 ± 4.3%) compared to the control group.

[Study on UV-Vis absorption spectra of tetra-azo-aromaticoxy substituted metallophthalocyanines].

UV-Vis absorption spectras of six series (18 kinds) of tetra- azo-aromaticoxy substituted metallophthalocyanines (R4 PcM, R = 4-pyridyloxy, 8-quinolinoxy, 2-methyl-8-quinolinoxy; substitution position: a position and beta position; M = Ni (II), Cu(II), Zn(II)) were measured. The effects of central mentals, the kinds and the positions of substitution groups, and solvents on the metallophthalocyanines' lamdamax in Q-band were discussed. Experimental data show: The lamdamax in Q-band of title complexes is about 680 nm. In contrast with substitution-free metallophthalocyanines(669-671 nm), the lamdamax in Q-band of the title complexes with the same central metal exhibits a different red-shift. The effect of substitution group's kinds on lamdamax in Q-band of the title complexes is more obvious in a position than in beta position, and with the same substitution group and central metal, lamdamax in Q-band of alpha position substituted complexes exhibits more obvious red-shift than beta position substituted complexes. The effects of central metal and solvent on lamda,ax in Q-band of the title complexes aren't obvious.