共查询到20条相似文献,搜索用时 15 毫秒
1.
J Bedwell P T Chatlani A J MacRobert J E Roberts H Barr J Dillon S G Bown 《Photochemistry and photobiology》1991,53(6):753-756
Radioprotective agents have been found to protect normal tissues during photodynamic therapy (PDT). We have investigated a phosphorylated thiol protectant WR-77913 (W7) with the photosensitizer aluminium sulphonated phthalocyanine (AISPc). We compared the effects of PDT on normal and tumour tissue in the rat colon, with and without this protectant. In normal colon no necrosis was seen in sites treated after administration of the W7. Necrosis of mean diameter 4.2 mm was seen in those given the protectant after light exposure. At tumour sites the area of necrosis was similar after light exposure before and after the administration of the protective agent. These results suggest a possible role for W7 in enhancement of selectivity of PDT action. Several mechanisms of protection against porphyrin phototoxicity by these drugs have been proposed, including acceleration of photobleaching. We used fluorescence to detect AISPc in strips of rat colon before and after laser treatment, with and without W7. However, a primary role for the photobleaching of AISPc as the mechanism for the protection shown is not supported by these observations. 相似文献
2.
Phthalocyanine 4 (Pc 4) is a promising photosensitizer currently in clinical trials. Photobiological responses to Pc 4 photodynamic therapy (Pc 4-PDT) have been characterized extensively, but relatively little has been done to evaluate dose metrics for this sensitizer. We describe an irradiation-induced increase in fluorescence in tumor cell monolayers. This increase is due solely to enhanced fluorescence from Pc 4, as confirmed by confocal spectroscopy. In EMT6 cells incubated with 250 nM Pc 4 for 24 h, the maximum increase in fluorescence is approximately 3.7-fold above baseline levels. This increase occurs over a range of fluences, 0.05-0.6 J cm(-2), where clonogenic survival decreases by 3 orders of magnitude. Light scattering measurements performed on similarly treated EMT6 cells in suspension suggested a Pc 4-PDT-mediated mitochondrial swelling of approximately 13% at 0.6 J cm(-2), where fluorescence enhancement saturates under these treatment conditions. Fluorescence imaging and light scattering experiments performed at a five-fold lower Pc 4 incubation concentration revealed a reduced fluorescence enhancement at a five-fold higher fluence, which produced comparable mitochondrial swelling. Taken together, these data suggest that Pc 4 is initially aggregated at high local concentration in mitochondria and that irradiation relaxes the quenching of Pc 4 fluorescence through a mechanism that may involve mitochondrial swelling. 相似文献
3.
J L McCullough G D Weinstein J L Douglas M W Berns 《Photochemistry and photobiology》1987,46(1):77-82
Systemic injection of hematoporphyrin derivative (HpD) in contribution with visible light (red or blue-green) delivered by laser was used to treat a patient with psoriasis. The psoriatic lesions responded vigorously to laser treatments, forming eschars by 1 week post irradiation. In contrast, only minimal erythema was observed in the noninvolved, clinically normal appearing skin. Two approaches for localized HpD administration were investigated in the guinea-pig and minipig models as a means of achieving local photodynamic effects. Intracutaneous injection of HpD produced localized cutaneous photosensitization with either UVA or red light. Azone increased percutaneous penetration of HpD in human skin in vitro. Topical application of HpD and irradiation with UVA produced localized cutaneous photosensitivity and inhibition of epidermal DNA synthesis. 相似文献
4.
David Kessel Kathryn Woodburn† Barbara W. Henderson C. K. Chang 《Photochemistry and photobiology》1995,62(5):875-881
Abstract— Localization and photodynamic efficacy of a monocationic porphyrin (MCP) were assessed using murine leukemia cells in culture. This sensitizer localized at surface membrane loci and catalyzed selective photodamage to membrane structures. Although both cationic and hydrophobic, this porphyrin was not recognized by the multidrug transporter, which excludes many cationic agents from cells that express multidrug resistance. Photodynamic studies with the murine radiation-induced fibrosarcoma tumor model indicated moderate photosensitization of neoplastic lesions in vivo at 3 h, but not at 24 h after sensitizer administration. Pharmacokinetic studies indicate that plasma levels, not tissue levels were the major determinant of photodynamic therapy (PDT) response. Consistent with this observation, vascular damage and disturbances of tissue perfusion followed PDT. These effects were more pronounced in tumor-bearing skin than in normal skin. The therapeutic response to MCP appeared to be related mainly to secondary, probably vascular, effects. 相似文献
5.
Nagy B Chiu SM Separovic D 《Journal of photochemistry and photobiology. B, Biology》2000,57(2-3):132-141
Photodynamic therapy with the phthalocyanine photosensitizer Pc 4 (Pc 4-PDT), an apoptosis inducer, is associated with accumulation of ceramide in various cell lines. The role of ceramide in Pc 4-PDT-induced apoptosis was investigated in A431 cells. Caspase-3 (casp-3) was activated and TUNEL positive cells began to appear 30 and 60 min post-Pc 4-PDT, respectively. A rapid increase (10 min) in cellular ceramide levels was observed after Pc 4-PDT. Induced ceramide accumulation was maintained over 60 min, Acid sphingomyelinase, a ceramide-generating enzyme, was inhibited after photosensitization with Pc 4, suggesting that the enzyme was not required for stimulated ceramide accumulation. Co-treatment of A431 cells with fumonisin B1, a ceramide synthase inhibitor, and Pc 4-PDT led to a decrease in ceramide levels without any effect on induced casp-3 activity or apoptosis. In the presence of zVAD, a pan-caspase inhibitor, apoptosis was abolished, while ceramide levels remained elevated after Pc 4-PDT. Exposure of A431 cells to exogenous C6-ceramide for 22 h, led to induction of apoptosis, and the process was abrogated by zVAD. In conclusion, C6-ceramide-, like Pc 4-PDT-induced apoptosis, is zVAD-sensitive. Furthermore, Pc 4 photosensitization can lead to apoptosis without FB-sensitive elevation in ceramide levels upstream of caspases. 相似文献
6.
Lihua Bai Jianxia Guo Franklin A. Bontempo III Julie L. Eiseman 《Photochemistry and photobiology》2009,85(4):1011-1019
The ability to noninvasively measure photosensitizer concentration at target tissues will allow optimization of photodynamic therapy (PDT) and could improve outcome. In this study, we evaluated whether preirradiation tumor phthalocyanine 4 (Pc 4) concentrations, measured noninvasively by the optical pharmacokinetic system (OPS), correlated with tumor response to PDT. Mice bearing human breast cancer xenografts were treated with 2 mg kg−1 Pc 4 iv only, laser irradiation (150 J cm−2 ) only, Pc 4 followed by fractionated irradiation or Pc 4 followed by continuous irradiation. Laser irradiation treatment was initiated when the tumor to skin ratio of Pc 4 concentration reached a maximum of 2.1 at 48 h after administration. Pc 4 concentrations in tumor, as well as in Intralipid in vitro , decreased monoexponentially with laser fluence. Pc 4-PDT resulted in significant tumor regression, and tumor response was similar in the groups receiving either fractionated or continuous irradiation treatment after Pc 4. Tumor growth delay following Pc 4-PDT correlated with OPS-measured tumor Pc 4 concentrations at 24 h prior to PDT ( R 2 = 0.86). In excised tumors, OPS-measured Pc 4 concentrations were similar to the HPLC-measured concentrations. Thus, OPS measurements of photosensitizer concentrations can be used to assist in the scheduling of Pc 4-PDT. 相似文献
7.
Cathy Y. Anderson Kristin Freye Karen A. Tubesing Ying-Syi Li Malcolm E. Kenney Hasan Mukhtar Craig A. Elmets 《Photochemistry and photobiology》1998,67(3):332-336
Photofrin® photodynamic therapy (PDT) has recently received FDA approval for the palliative treatment of to-tally and partially obstructing esophageal malignancies. However, there is a need for new PDT photosensitizers because Photofrin has a number of undesirable features. The purpose of this study was to evaluate the efficacy of four amine-bearing silicon phthalocyanines—Pc4, Pc10, Pc12 and Pc18—as potential PDT photosensitizers. Equimolar concentrations of these Pc were found to be highly effective at causing the regression of RIF-1 tumors trans-planted to C3H/HeN mice. The amount of Pc4 necessary to cause an equivalent amount of tumor regression in this model system was substantially less than the amount of Photofrin. The cutaneous phototoxicity of the silicon Pc photosensitizer was assessed by the utilization of the murine ear-swelling model. When C3H mice were exposed to 167 J/cm2 of polychromatic visible light from a UVB-filtered solar simulator, which emitted UV radiation and visible light above 320 nm, the Pc produced little, if any, cutaneous photosensitivity. These results indicate that Pc4, Pc10, Pc12 and Pc18 are at least as effective as Photofrin in PDT protocols, while at the same time addressing many of the drawbacks of Photofrin. 相似文献
8.
Ying Jt. Diana Walstad J. Tony Brown Stephen K. Powers 《Photochemistry and photobiology》1992,56(3):385-390
The effectiveness of intratumoral photoradiation in photodynamic therapy (PDT) using a polyporphyrin photosensitizer was studied in the RT-2 rat glioma model. One week after intracerebral implantation of RT-2 cells, experimental rats received a single i.p. injection of 2 mg/kg of Photofrin. After administration of the photosensitizer (48 h), the tumors were partially resected and the exposed cavity was irradiated with 15 J of laser light at a wavelength of 630 nm. Further treatment with a large craniectomy significantly enhanced rat survival. Control rats which received no photosensitizer but were treated with surgery, alone or in combination with laser irradiation, succumbed from early tumor recurrence. Photodynamic therapy without decompressive surgery resulted in hemorrhagic infarction of residual tumor and adjacent brain with focal cerebral edema which resulted in cerebral herniation and early death. Our results indicate that photodynamic therapy is effective in treating residual brain tumor but at the expense of brain tissue surrounding the tumor. Unless relieved, intracranial pressure from photodynamic therapy-associated cerebral edema in this animal model resulted in shortened survival. 相似文献
9.
Uzdensky A Bragin D Kolosov M Dergacheva O Fedorenko G Zhavoronkova A 《Photochemistry and photobiology》2002,76(4):431-437
To study the mechanism of photodynamic nerve cell killing, isolated crayfish mechanoreceptor neurons were photosensitized by the sulfonated aluminum ophthalocyanine Photosens. Neuron activity was continuously recorded until irreversible abolition. Intense (10(-5) M Photosens) or weak (10(-7) M Photosens) photosensitization induced different bioelectric neuron responses: firing activation followed by irreversible depolarization block or gradual inhibition until firing abolition, respectively. These bioelectric responses were accompanied by different biochemical and morphological changes. In the case of intense photosensitization, neuron nuclei swelled and then shrank. Succinate dehydrogenase (SDH) was inhibited, and the plasma membrane was compromised just after firing cessation. Weak photosensitization did not induce these changes but caused swelling of the endoplasmic reticulum and destruction of the matrix, cristae and membranes in some of the mitochondria. Other mitochondria, however, retained the normal structure. Plasma membrane damage, SDH inhibition, nucleus shrinkage and impairment of the nuclear border occurred after 2-4 h. It is concluded that intense photosensitization induced necrotic processes during irradiation, whereas weaker impact caused delayed necrosis 2-4 h later. The observed electrophysiological neuron responses to photodynamic therapy may be considered as early hallmarks of different modes of forthcoming cell death. 相似文献
10.
Allen CM Langlois R Sharman WM La Madeleine C Van Lier JE 《Photochemistry and photobiology》2002,76(2):208-216
Photodynamic therapy (PDT) is a promising treatment modality that has recently been accepted in clinics as a curative or palliative therapy for cancer and other nonmalignant conditions. Phthalocyanines (Pc) are attractive photosensitizers for PDT because of their enhanced photophysical and photochemical properties. The overall charge and solubility of Pc play a major role in their potential usefulness for PDT. A series of amphiphilic derivatives of tetrasulfonated aluminum Pc (AlPcS4) was prepared by substituting one of the four sulfonate groups with aliphatic side chains of 4, 8, 12 and 16 carbon atoms. The photodynamic properties of the derivatives were compared with those of AlPcS4 and the adjacent disulfonated aluminum Pc. Parameters studied included reversed-phase high-performance liquid chromatography (HPLC) retention times, capacity to generate singlet oxygen (1O2), in vitro cell uptake and phototoxicity, as well as PDT response of transplantable EMT-6 tumors in mice. The monomerized AlPcS4 derivatives showed similar or higher capacities to generate 1O2 as compared with the parent AlPcS4 as measured from relative L-tryptophan photooxidation yields. A549 cell uptake of the AlPcS4 derivatives decreased in the following order: AlPcS4(C16) > AlPcS4(C12) > AlPcS4(C8) > AlPcS4(C4). Human low-density lipoprotein at high concentrations (40 micrograms/mL) completely prevented uptake, whereas at 4 micrograms/mL uptake was decreased for the more lipophilic compounds and yet remained unaffected for the more hydrophilic dyes. Using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, A549 cell survival was assessed; it showed that photocytotoxic activity varied directly with the HPLC retention times, i.e. more hydrophilic compounds were less phototoxic. As 1O2 yields were similar for the four substituted AlPcS4 derivatives, it was postulated that the increased cytotoxic activity was caused by enhanced subcellular localization as a result of the long aliphatic side chains. These amphiphilic compounds proved to be photodynamically potent against the EMT-6 mouse mammary tumor model implanted in Balb/c mice. At dye doses of 0.2 mumol/kg and a fluence of 400 J/cm2 complete tumor regression was observed with no morbidity. The substitution of AlPcS4 with long aliphatic chains on the macrocycle greatly enhances its photodynamic efficacy both in vitro and in vivo. 相似文献
11.
Jean-Yves Matroule Anne-Cecile Hellin Patrice Morliere A.-S. Fabiano Rend Santus Marie-Paule Merville Jacques Piette 《Photochemistry and photobiology》1999,70(4):540-548
Aminopyropheophorbide (APP) is a second generation of photosensitizer for photodynamic therapy (PDT). We demonstrated that APP strongly absorbed red light and, after being taken up by colon cancer cells (HCT-116 cells), was localized in cytoplasmic and internal membranes but not in mitochondria. The APP-mediated photosensitization was cytotoxic for HCT-116 cells through an induction of apoptosis. Indeed, DNA fragmentation (DNA laddering and terminal deoxyuridine nick-end labeling) and chromatin condensation (4',6-diamidine-2'-phenylindole staining) could be visualized soon after photosensitization. Because nuclear factor (NF)-kappa B is involved in the response to many photosensitizers, we also demonstrated its nuclear translocation in two waves: a rapid and transient one, followed by a slow and sustained phase. The NF-kappa B turned out to be involved in an antiapoptotic response to APP-mediated photosensitization because the HCT-116 cell line expressing the dominant negative mutant of inhibitor-kappa B alpha was more sensitive to apoptosis as measured by DNA fragmentation and caspase activation. These data unambiguously show that a membrane-located photosensitizer can lead to effective apoptosis, reinforcing the idea that PDT can be an effective means to eradicate colon cancer cells. 相似文献
12.
Cubeddu R Canti G D'Andrea C Pifferi A Taroni P Torricelli A Valentini G 《Journal of photochemistry and photobiology. B, Biology》2001,60(2-3):73-78
Time-resolved reflectance spectroscopy was performed on tumor-bearing mice, administered with disulphonated aluminum phthalocyanine (AlS(2)Pc, 5 mg/kg body weight), before, during and after photodynamic therapy. This allowed us to evaluate the absorption spectrum of AlS(2)Pc in vivo from 610 to 700 nm, and to investigate how the therapeutic irradiation affects it. Two tumor locations (intraderma on the back and intramuscular in the leg), and two uptake times (3 and 12 h) were considered. As already observed previously, the absorption spectrum of AlS(2)Pc in vivo is centered at 680-685 nm. The irradiation causes a blue-shift of the measured line shape, more or less marked depending on the experimental conditions. A reduction in absorption is also often observed upon illumination with therapeutic light doses. 相似文献
13.
Cynthia M. Allen Wesley M. Sharman Carole La Madeleine Joseph M. Weber Réjean Langlois Réné Ouellet Johan E. van Lier 《Photochemistry and photobiology》1999,70(4):512-523
A brief summary of the mechanisms involved in photodynamic therapy (PDT) and the role of delivery vehicles for photosensitizer targeting is addressed. Phthalocyanines (Pc) have been coupled to adenovirus type 2 capsid proteins including the hexon, the penton base and the fiber to enhance their target selectivity. Adenovirus penton base proteins contain the arginine-glycine-aspartic acid peptidic sequence (RGD) motif known to bind with great affinity and high specificity to integrin receptors, expressed by several types of cancer. Tetrasulfonated aluminum phthalocyanine (AlPcS4) was covalently coupled to the various capsid proteins via one or two caproic acid spacer chains (A1 or A2) in 7:1 up to 66:1 molar ratios. The capacity of the bioconjugates for singlet oxygen production, as measured by an L-tryptophan oxidation assay, was strongly reduced, likely reflecting scavenging by the carrier. Cell adsorption and in vitro photocytotoxicity assays were carried out using the A549 and HEp2 human cell lines expressing integrin receptors, and one murine, the EMT-6 cell line, which lacks receptors for the RGD sequence. The AlPcS4A2-protein complexes induced greater cytotoxicity as compared to the analogous AlPcS4A1 preparations. The penton base-AlPcS4A2 derivative was the more phototoxic for all cell lines tested. Tumor response studies using Balb/c mice with EMT-6 tumor implants demonstrated that the free AlPcS4A2 induced complete tumor regression at a dose of 1 mumol/kg and 400 J/cm2, which is comparable to the activity of the known AlPcS2adj. A mixture of adenovirus type 2 soluble proteins covalently labeled with AlPcS4A2 required 0.5 mumol/kg to induce the same response with the same light dose, suggesting that the high affinity RGD/receptor complex is able to target Pc for PDT. 相似文献
14.
N C Yates J Moan A Western 《Journal of photochemistry and photobiology. B, Biology》1990,4(4):379-390
Metal naphthalocyanine complexes (MNCSs) absorb light in the near-IR spectral region (760 nm) where tissue penetration is optimal and they have been proposed as agents for photodynamic therapy (PDT). Sulphonated derivatives of tris-(2,3-naphthalocyanato) bis-chloroaluminium(III) and zinc(II) with various degrees of sulphonation were prepared. Cellular uptake, aggregation in cellular environments, cytotoxicity and photosensitizing properties were studied. Three of the four dyes studied were taken up by cells to a satisfactory degree and were not cytotoxic at the concentration used (10 micrograms ml-1). The least sulphonated sample of zinc naphthalocyanine produced some phototoxic effects (LD50 = 1.12 J cm-2). All the other samples of sulphonated naphthalocyanine were found to be aggregated inside the NHIK 3025 cells, preventing any significant PDT effect. 相似文献
15.
Syed I. A. Zaidi Rajesh Agarwal Guido Eichler Boris D. Rihter Malcolm E. Kenney Hasan Mukhtar 《Photochemistry and photobiology》1993,58(2):204-210
Abstract— Photodynamic therapy (PDT) of cancer is a modality that relies upon the irradiation of tumors with visible light following selective uptake of a photosensitizer by the tumor tissue. There is considerable emphasis to define new photosensitizers suitable for PDT of cancer. In this study we evaluated six phthalocyanines (Pc) for their photodynamic effects utilizing rat hepatic microsomes and human erythrocyte ghosts as model membrane sources. Of the newly synthesized Pc, two showed significant destruction of cytochrome P-450 and monooxygenase activities, and enhancement of lipid peroxidation, when added to microsomal suspension followed by irradiation with ∼ 675 nm light. These two Pc named SiPc IV (HOSiPcOSi[CH3 ]2 [CH2 ]3 N[CH3 ]2 ) and SiPc V (HOSiPcOSi[CH3 ]2 [CH2 ]3 N[CH3 ]3 1 I) showed dose-dependent photodestruction of cytochrome P-450 and monooxygenase activities in liver microsomes, and photoenhancement of lipid peroxidation, lipid hydroperoxide formation and lipid fluorescence in rnicrosomes and erythrocyte ghosts. Compared to chloroaluminum phthalocyanine tetrasulfonate, SiPc IV and SiPc V produced far more pronounced photodynamic effects. Sodium azide, histidine, and 2,5-dimethylfuran, the quenchers of singlet oxygen, afforded highly significant protection against SiPc IV- and SiPc V-mediated photodynamic effects. However, to a lesser extent, the quenchers of superoxide anion, hydrogen peroxide and hydroxyl radical also showed some protective effects. These results suggest that SiPc IV and SiPc V may be promising photosensitizers for the PDT of cancer. 相似文献
16.
Rajesh Agarwal Mohammad Athar Craig A. Elmets David R. Bickers Hasan Mukhtar 《Photochemistry and photobiology》1992,56(1):43-50
Photodynamic therapy (PDT) of cancer combines irradiation of tumors with visible light following selective uptake of the photosensitizer by the tumor cells. PhotofrinR-II (Pf-II) is the only photosensitizer which is in clinical use in PDT, whereas chloroaluminum phthalocyanine tetrasulfonate (AlPcTS) has also shown promise in preclinical studies. In most such studies, the effectiveness of the photosensitizers has been assessed in implanted tumor model systems rather than in model systems where tumors are allowed to grow in their own connective tissue matrix. In this study the pharmacokinetics, tumor ablation capability and cutaneous photosensitization response of AlPcTS have been assessed in mice bearing chemically- and ultraviolet B radiation (UVB)-induced benign skin papillomas. When tumor-bearing animals were injected intraperitoneally with AlPcTS (5 mg/kg body wt), maximum tumor:normal skin ratio of 2.4 was observed at 48 h, at which time the mice were irradiated within the absorption spectrum of the photosensitizer. In tumor ablation studies with SENCAR mice bearing chemically-induced skin tumors, AlPcTS resulted in greater than 80% ablation in tumor volume at 20 days post-irradiation. In cutaneous photosensitization response, AlPcTS produced only transient effects (no effect after 24 h) in SENCAR mice. Pharmacokinetics data, tumor ablation effects and cutaneous photosensitization response of AlPcTS were comparable in SKH-1 hairless mice bearing UVB-induced skin tumors. Our data indicate that AlPcTS produces significant photodynamic effects towards the ablation of murine skin tumors, and that it does not produce prolonged cutaneous photosensitivity. 相似文献
17.
Ke MS Xue LY Feyes DK Azizuddin K Baron ED McCormick TS Mukhtar H Panneerselvam A Schluchter MD Cooper KD Oleinick NL Stevens SR 《Photochemistry and photobiology》2008,84(2):407-414
To examine the clinical applicability of Pc 4, a promising second-generation photosensitizer, for the photodynamic treatment of lymphocyte-mediated skin diseases, we studied the A431 and Jurkat cell lines, commonly used as surrogates for human keratinocyte-derived carcinomas and lymphocytes, respectively. As revealed by ethyl acetate extraction and absorption spectrophotometry, uptake of Pc 4 into the two cell lines was linear with Pc 4 concentration and similar on a per cell basis but greater in Jurkat cells on a per mass basis. Flow cytometry showed that uptake was linear at low doses; variations in the dose-response for uptake measured by fluorescence supported differential aggregation of Pc 4 in the two cell types. As detected by confocal microscopy, Pc 4 localized to mitochondria and endoplasmic reticulum in both cell lines. Jurkat cells were much more sensitive to the lethal effects of phthalocyanine photodynamic therapy (Pc 4-PDT) than were A431 cells, as measured by a tetrazolium dye reduction assay, and more readily underwent morphological apoptosis. In a search for molecular factors to explain the greater photosensitivity of Jurkat cells, the fate of important Bcl-2 family members was monitored. Jurkat cells were more sensitive to the induction of immediate photodamage to Bcl-2, but the difference was insufficient to account fully for their greater sensitivity. The antiapoptotic protein Mcl-1 was extensively cleaved in a dose- and caspase-dependent manner in Jurkat, but not in A431, cells exposed to Pc 4-PDT. Thus, the greater killing by Pc 4-PDT in Jurkat compared with A431 cells correlated with greater Bcl-2 photodamage and more strongly to the more extensive Mcl-1 degradation. Pc 4-PDT may offer therapeutic advantages in targeting inflammatory cells over normal keratinocytes in the treatment of T-cell-mediated skin diseases, such as cutaneous lymphomas, dermatitis, lichenoid tissue reactions and psoriasis, and it will be instructive to evaluate the role of Bcl-2 family proteins, especially Mcl-1, in the therapeutic response. 相似文献
18.
David Kessel Kevin M. Smith R. K. Pandey F.-Y. Shiau Barbara Henderson 《Photochemistry and photobiology》1993,58(2):200-203
Abstract— Biophysical and photobiological properties of a group of bacteriochlorins were compared with efficacy of these products for photodynamic therapy of murine tumors. Predictive factors for selective photosensitization in vivo include affinity binding to lipoproteins greater than albumin, extinction coefficient at the wavelength of irradiation and tumor/skin distribution. Efficacy was correlated with circulating plasma levels of the different sensitizers but not with the photodynamic therapy response in cell culture. 相似文献
19.
Leishmania were previously shown to undergo photolysis when their transgenic mutants were induced endogenously to accumulate cytoplasmic uroporphyrin or when loaded exogenously with aluminum phthalocyanine chloride. A combinational use of both is reported here, which renders Leishmania far more susceptible to photolysis. Fluorescence microscopy of cells loaded with the two photosensitizers localized them to different subcellular sites. Pre-exposure of Leishmania to both synergistically sensitized them for photolysis as extracellular promastigotes and intracellular amastigotes in infected macrophages in vitro when illuminated at specific wavelengths to excite the respective photosensitizers for production of reactive oxygen species. Both Leishmania stages lost their viability completely when doubly photosensitized optimally and illuminated at low intensity, the host cells being left unscathed. Inoculation of mice with photoinactivated Leishmania produced no lesions, which invariably developed in the control groups during a period of observations for 8 weeks. Pretreatment of Leishmania with both photosensitizers rendered these cells susceptible to clearance from the ear dermis by white light illumination. The results suggest that double photosensitization for synergistic activity enhances the efficacy and safety of photodynamic therapy in general and for Leishmania in particular. 相似文献
20.
E Ben-Hur R C Hoeben H Van Ormondt T M Dubbelman J Van Steveninck 《Journal of photochemistry and photobiology. B, Biology》1992,13(2):145-152
The photodynamic inactivation of retroviruses was investigated using aluminium and zinc phthalocyanine (Pc) derivatives. The N2 retrovirus packaged in either of the two murine cell lines, Psi2 and PA317, was used as a model for enveloped viruses. AlPc derivatives were found to be more effective photodynamically for inactivation of the viruses than the corresponding ZnPc derivatives. Sulphonation of the Pc macrocycle reduced its photodynamic activity progressively for both AlPc and ZnPc. Fluoride at 5 mM during light exposure completely protected viruses against inactivation by AlPc. In the presence of F-, inactivation by the sulphonated derivatives AlPcS1 and AlPcS4 was reduced 2.5- and twofold respectively. In a biological membrane (erythrocyte ghosts), F- had no significant effect on AlPcS4-sensitized lipid peroxidation. Under similar conditions, cross-linking of spectrin monomers in ghosts is drastically inhibited (E. Ben-Hur and A. Orenstein, Int. J. Radiat. Biol., 60 (1991) 293-301). Since Pc derivatives do not inactivate non-enveloped viruses, it is hypothesized that inactivation occurs by photodynamic damage to envelope protein(s). Substitution of sulphonic acid residues reduces the binding of Pc derivatives to the envelope protein(s), thereby diminishing their photodynamic efficacy and the ability of F- to modify it. 相似文献