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Objective To investigate and compare the killing effect of photodynamic therapy (PDT)induced by hematoporphyrin derivative (HpD),hematoporphyrin monomethyl ether (HMME) and photocarcinorin (PsD007) on human leukemia cells K562 in vitro.Methods Human leukemia cells were cultured with serial concentrations of photosensitizers followed by irradiation of different dosage of laser light,then MTT colorimetric assay was applied to measure the relative survival rate of PDT for the cells.Results Significant difference in the inhibitory between the PDT group and control group was observed (P＜0.05).The survival rate of PDT for the cells elevated along with the increase in the concentration of sensitizer and dose of laser light.When the photosensitizer concentration was bigger (25 μg/ml) or the energy density was bigger (7.2 J/cm2),the effect of PsD007 was better than HMME,and they were significantly better than HpD (P＜0.05).Conclusion PDT has significant killing effect on human leukemia cells K562,and its relative inhibitory rate appears to be correlated with the dose of sensitizer and laser light irritation.The effect of PDT is related to the photosensitizers.The effect of HpD-PDT is not as effective as PsD007 and HMME.On the conditions of higher energy density and larger photosensitizer concentration,the effect of PsD007-PDT is better than HMME-PDT.
ABSTRACT
In this paper, we describe a synergistic effect of hyperthermia on photocarcino-rin photodynamic therapy. The results suggest that the synergistic action of hyperthermia and photodynamic reaction was markedy better than that of hyperthermia alone plus photocarcinorin alone. with hyperthermia treatment (42℃, 30 min) alone, the fraction of cells inactivated was 7%, while with photodynamic effect alone(1J/cm2) that was 30% (?5%).when the same dosage of irradiation was applied after a rise in temperature, the fraction of cells inactivated increased to 80% (?5%) and when temperature was raised to the same amount after irradiation the fraction of cells inactivated increased to 92%. It can be seen that hyperthermia enhances, the response of tumor cells to photocarcinorin photodynamic effect in a synergistic way.
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5.16 log of K562, U937, HIMeg and HL60 cells, respectively, but spare 23.37 ? 25.66% of normal CFU-GM (0.63 log killing). When HL60 cells mixed with normal mononucleated bone marrow cells in 1:9 ratio were studied, the killing of HL60 colonies was more than 4.29 log. The result suggested that photocarcinorin plus light could eliminate leukemic progenitors, and might be used in clinical ABMT. Several factors that might affect the photosensitization effect on cells were discussed.
ABSTRACT
Preclinical toxicology of PsD-007(a new photosensitizer prepared in our coll-ege)was studied.Pathological observations were performed on major organs of the toxic dogs including liver, kidneys, myocardium, lungs, spleen, stomach, intestine, mesenteric lymph nodes, urinary bladder, prostata, testes, ovary, adrenals, pituitary gland, thyroid and brain.Focal balloning degeneration of hepatic cells occurred in lower dose groups, and degeneration and necrosis of hepatocytes and proximal convoluted tubular epithelial cells of kidney, and edema of brain in higher dose groups were observed in acute toxicity testing.The hepatocytes were normal, but hyperplasia, swelling and vacuoles within the cytoplasm of the Kupffers cells in liver, necrosis of tubules of kidney and edema of brain in higher dose groups were found in subacute testing. These damages were reversible within 4 weeks except in higher dose groups, and their morphologic severity was dose-related.The results show that the liver and kidney may be the main target organs of toxicity of PsD, and the detections of hepatic and renal functions may be useful to guard against its toxic effects during clinical use.
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The clinical pharmacokinetic behavior of new photosensitizer photocarcinorin for the photoradiation therapy of 11 patients with different malignant tumors was studied by means of fluorospectrophotometric method after intravenous infusion.The dose infused was 4-4.5 mg/kg body weight and the infusion rate, 0.1 mg/ kg/min.It is a three-compartment model as determined by the drug-time curve through Akaike's Information Criterion(AIC) .The principal pharmacokinetic parameters calculated by nonlinear least-square regression program are: t1/2? = 0.26?0.05h, t1/2? = 4.52?1.04h, t1/2?=32.9?5.31h.In addition, the pharmacokinetic parameters of one patient injected with lower dose(1.82 mg/kg)were also determined, and shown as a three compartment model.
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The chemical composition, separation and identification of the components as well as the tumor photobiological activities of the major components of the new tumor-photochemodiagnostic and photochemotherapeutic agent photocarcinorin (PsD-007) were represented in this paper. It has been shown by the results of HPLC analysis in combination with spectroscopic determinations that PsD-007 is composed of 7 different porphyrins: MHD, DMD, MVD, AHD, HVD, Hp and Pp. The experimental results show that MHD, DMD and MVD are the major tumor photobiologically active components of PsD-007.
ABSTRACT
The preparation,chemical composition and physicochemical properties of photocar-cinorin (PsD-007),a new drug of photolocalizaion and photochemotherapy for human malignancies,are reported here.It has been shown by the resul s of thin layer and high performance liquid chromatographic (TLC & HPLC) analyses that about 85% of its total weight are relatively hydrophobic porphyrins of unknown structure in which a fraction with the same retention time as .hematoporphyrin(Hp)monoacetate constituts over 60%.There are also 4.2% of Hp,8.6% of 3(8) hydroxycthy lS-(3)-vinyldcutero-porphyrin (HVD) and 0.6% of portoporphyrin (Pp) in this drug.The presence and amount of HVD in PsD-007 were determined by an authentic sample prepared in our laboratory.The changes of the composition of PsD-007 on exposure to different doses of argon laser (488+ 514.5nm) were detected by HPLC.The variations in Soret peak of UV absorption spectra of PsD-007 protected from light at a constant temperature were also determined
ABSTRACT
The results of observation on experimental photolocalization and photochemotherapy with a new drug photocarcinorin (PsD-007) and argon laser (514.5+ 488nm) for different transplanted animal tumors are reported.The interrelationship among the dose of light irradiation,dose level of the drug and the efficiency of experimental photodiagnosis and photochemotherapy for animal tumors was studied.It has been shown that the degree of photodynamic damage on tumors is proportional to the light dose.The upper and lower thresholds of effective light-dose seem to be about 150 mw/cm2 and 40 mw/cm2 for 30 min respectively.The light dose for curing half of experimental animals ranged from 80 to 100 mw/cm2 for 30 min with a drug dose of 5mg/kg.The photodynamic damage on tumors in closely correlated to drug dose with a given light dose.The photodynamic effects on different tumors are essentially consistent with each other.A bright oranged-red fluorescence appeared on the fumor tissues of S180 sarcoma,Lewis lung carcinoma or U14 cervical carcinoma bearing mice on exposure to argon laser and/or UV light (365nm) 24 and 48 h after the injection of 5mg/kg of PsD-007.But no fluorescence was found on the normal tissues around the tumors under the same conditions.It is suggested that PsD-007 may be specifically uptaken into the malignant tissues.The intensity of fluorecence on tumors is directly proportional to drug dose and inversely proportional to the time interval between drug administration and observation on the fluorescence.The homogeneity of distribution of light energy was improved by using a "lens aperture" placed between the light source and irradiated animal.A model system was thus provided for the evaluation of the efficiency of drugs in the photochemodiagnosis and photochemotherapy for animal tumors.
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A comparative study on photodynamic effects of photocarcinorin (PsD-007) and photofrin II on human cancer cells was under taken.The results show that the photo-dynamic effects of PsD-007 on human liver cancer cells SMMC-7721 and human gastric cancer cells NGCC-8310 were slightly better than or at least the same as those of photofrin Ⅱ after treatment with the same dosage of the two photosensiti-' zers and light.This experiment suggests that the photodynamic effects of killing human cancer cells increase with light dose within a given dosage of the photosensi-tizers,while within a certain dosage of the photosensitizers and light radiation,they increase with the dosage of the two photosensitizers.
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The factors which had an influence on the phototoxic effect of the photocarcino-rin were studied in mice.The phototoxic reaction was correlated with the doses of the drug and irradiation time.The phototoxic reaction did not develop in mice by topical administration of the drug in ears or when there was an interval (72h) between intravenous injection and irradiation.