Li-Jun Zhang

Photodynamic efficiency of a chlorophyll-a derivative in vitro and in vivo.

This paper reports the antitumor activity of a chlorophyll-a derivative, 2-[1-hydroxyethyl]-2-devinylpyropheophorbide-a (HEPa). Photophysical characteristics of HEPa were measured. And its cytotoxicity, intracellular localization, biodistribution, efficiency of photodynamic therapy (PDT), histological analysis were investigated using human bile duct carcinoma cells (QBC-939) and QBC-939 tumor bearing BABL/c nude mice as animal model. The results showed that HEPa was localized mainly within the cytoplasmic region and partially in lysosome. Biodistribution of HEPa in QBC-939 tumor bearing BABL/c nude mice showed its fast rate of clearance and high tumor selectivity. In vitro, HEPa had low dark toxicity and high photoxicity against QBC-939 cells. The inhibition rate of QBC-939 tumor could increase up to 92.3%, and H&E staining confirmed that HEPa could cause serious damage to the tumor with light dose of 100J/cm(2), implying that HEPa has potential to be a new antitumor candidate for photodynamic therapy (PDT).

Antitumor effects evaluation of a novel porphyrin derivative in photodynamic therapy

In this paper, the antitumor activity of a novel porphyrin-based photosensitizer 5,10,15,20-tetrakis[(5-diethylamino)pentyl] porphyrin (TDPP) was reported in vitro and in vivo. The photophysical and cellular properties of TDPP were investigated. The singlet oxygen generation quantum yield of TDPP was detected; it showed a high singlet oxygen quantum yield of 0.52. The intracellular distribution of photosensitizer was detected with laser scanning confocal microscopy. The efficiency of TDPP-photodynamic therapy (PDT) in vitro was analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and in situ trypan blue exclusion test. Treated with a 630-nm laser, TDPP can kill cultured human esophageal cancer cell line (Eca-109) cells and reduce the growth of Eca-109 xenograft tumors significantly in BABL/c nude mice. And histopathological study was also used to confirm the antitumor effect. It has the perspective to be developed as a new antitumor drug in photodynamic therapy and deserves further investigation.

Anti-tumor activities of a novel chlorin derivative for photodynamic therapy in vitro and in vivo

In this study, a novel photosensitizer meso-tetra (3-pyrrolidinomethyl-4-methoxyphenyl) chlorin (TPMC) was reported. It displays a characteristic long wavelength absorption peak at 656 nm and it shows a singlet oxygen quantum yield of 0.48. After light irradiation with 650 nm laser, it can kill Eca-109 and SMMC-7721 cells in vitro (25 mW/cm2, 1.2 to 3.6 J/cm2) and destroy Eca-109 tumor in nude mice (50 mW/cm2, 90 J/cm2). It has the perspective to be developed as a new anti-tumor drug in photodynamic therapy (PDT) photodiagnosis, and deserves further investigation.

Synthesis, characterization and biological evaluation of a novel biscarboxymethyl-modified tetraphenylchlorin compound for photodynamic therapy

A novel photosensitizer trans-2,3-dihydro-2,3-bis(carboxymethyl)-5,10,15,20-tetraphenylchlorin (BCTC) was synthesized. Its photophysical and photochemical properties, intracellular localization, photocytotoxicity in vitro and vivo were also investigated. BCTC displays a characteristic long wavelength absorption peak at 652 nm and shows a singlet oxygen quantum yield of 0.68 in DMF. Without light activation, BCTC was nontoxic to human esophageal cancer cells. However, upon light activation, BCTC exhibited significant photocytotoxicity. After PDT treatment, the growth of Eca-109 tumor in nude mice was significantly inhibited. This study suggests that BCTC is an effective photosensitizer for PDT to tumors.

Antitumor activity evaluation of meso-tetra (pyrrolidine substituted) pentylporphin-mediated photodynamic therapy in vitro and in vivo.

Photodynamic therapy is a minimally invasive and promising new method in cancer treatment and has attracted considerable attention in recent years. An ideal photosensitizer is a crucial element to photodynamic therapy. In the present paper, a novel porphyrin derivative, 5, 10, 15, 20-tetrakis (5-(pyrrolidin-1-yl) pentyl) porphin (TPPP) was synthesized. Its spectroscopic and physicochemical properties, therapeutic efficacy as a photosensitizer in photodynamic therapy for human bladder cancer in vitro and in vivo were investigated. TPPP had strong absorption at 648nm (ε=1.75×10(4)M(-1)cm(-1)), and two fluorescence emission peaks at 652nm and 718nm. PDT with TPPP showed low dark toxicity and high phototoxicity to human bladder cancer T24 cells in vitro. In bearing T24 tumor nude mice, the growth of tumor was significantly inhibited by combining use of 5mg/kg TPPP with 100J/cm(2) (650nm, 180mW/cm(2)) laser irradiation at 3h following injection of TPPP. The antitumor effect was also confirmed with histopathological assay. The histopathological study results revealed that PDT using TPPP and 100J/cm(2) (650nm, 180mW/cm(2)) laser irradiation induced tumor cells shrunken and necrotic. These results indicate that TPPP is useful as a new photosensitizer in PDT for cancer, and deserves further investigation.

Synthesis, photophysical properties and biological evaluation of β-alkylaminoporphyrin for photodynamic therapy.

A series of β-alkylaminoporphyrins conjugated with different amines at β position (D1-D3) or with electron-donating and electron-withdrawing substituents at phenyl position (D4-D6) were synthesized. Their photophysical and photochemical properties, intracellular localization, photocytotoxicities in vitro and vivo were also investigated. All target compounds exhibited no cytotoxicities in the dark and excellent photocytotoxicities against HeLa cells. Among them, D6 showed the highest phototoxicity and the lowest dark toxicity, which was more phototoxic than Hematoporphyrin monomethyl ether (HMME). In addition, D6 exhibited best photodynamic antitumor efficacy on BALB/c nude mice bearing HeLa tumor. Therefore, D6 is a powerful and promising antitumor photosensitizer for photodynamic therapy.

Inhibition of Laser-Induced Choroidal Neovascularization by Hematoporphyrin Dimethylether-Mediated Photodynamic Therapy in Rats

This study aimed to investigate the effect of hematoporphyrin dimethylether (HDME)-mediated photodynamic therapy for laser-induced choroidal neovascularization (CNV) in adult Brown Norway rats. HDME was administered via tail vein at 14 d after the laser photocoagulation, and the rats received irradiance with a laser light at 570 nm at 15 min after injection. CNV was evaluated by fundus photography, fundus fluorescein angiography, optical coherence tomography, and hematoxylin and eosin staining. We found that CNV was occurred at 7 d after photocoagulation and reaching peak activity at 14 d after photocoagulation. There is a significant reduction in the total area of the fluorescein leakage and the number of strong fluorescein leakage spots on 7 d after HDME-mediated photodynamic therapy (PDT). The results suggest that HDME-mediated PDT inhibits laser-induced CNV in rats, representing a promising therapy for wet age-related macular degeneration.