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Giulio Jori

Publications and source records attributed to Giulio Jori.

27 records · Page 2Linked to original sources
PubMed2002

Low-density lipoprotein receptors in the uptake of tumour photosensitizers by human and rat transformed fibroblasts.

Low-density lipoproteins (LDL) increase the selectivity of tumour targeting by drugs, including sensitisers for photodynamic therapy, because of the enhanced expression of specific LDL receptors in many types of transformed as compared with non-transformed cells. This investigation aims at gaining more information on the role of LDL receptors in the accumulation of photosensitizer-LDL complexes by human and rat transformed fibroblasts, and the interference of the photosensitizer with LDL recognition by the specific receptors. Both an amphiphilic hematoporphyrin IX (Hp) and a hydrophobic Zn(II)-phthalocyanine (ZnPc) photosensitizers bind to human LDL with molar ratios of 5-6:1 and 10-12:1, respectively. The hematoporphyrin-LDL complex is accumulated by human HT1080 fibroblasts mainly through the high affinity LDL receptors, while the Zn-phthalocyanine-LDL complex is internalised through non specific endocytosis because of changes in the apoB LDL structure induced by phthalocyanine association, as suggested by spectroscopic studies. The uptake of LDL-delivered hematoporphyrin, but not Zn-phthalocyanine, is about 4-fold higher in HT1080 cells stimulated for maximal expression of LDL receptors as compared with non-stimulated cells. This difference is abolished by LDL acetylation. Human LDL-bound hematoporphyrin and Zn-phthalocyanine are up taken by stimulated and non-stimulated 4R rat fibroblasts with similar efficiency. Scatchard plot analysis of human (125)I-LDL binding to 4R cells shows the presence of only low affinity receptors while 350,000 high affinity receptors are expressed per HT1080 cell. It is concluded that a careful evaluation of the lack of conformational changes of LDL is critical for guaranteeing the selectivity and efficiency of photosensitizer delivery to tumour cells.

Animals↗
PubMed2002

Photosensitization of Colpoda inflata cysts by meso-substituted cationic porphyrins.

Colpoda inflata cysts accumulate significantly large amounts of meso-substituted cationic porphyrins, including meso-tetrakis(N-methyl-4-pyridyl)porphine (TMP-C1) and its mono-N-methyldecyl (TMP-C10) and -tetradecyl (TMP-C14) analogues upon incubation for 1 h with 1-48 microM porphyrin concentrations. All three porphyrins at concentrations greater than 10 microM exhibited a significant toxicity toward the cysts, in particular lowering the degree of excystment. Upon visible light irradiation of the porphyrin-loaded cysts, extensive photodamage was observed even in the presence of 1 microM porphyrin, as shown by light microscopy observations and counting of vegetative emerging cells The presence of one decyl or tetradecyl hydrocarbon chain caused about 10-fold enhancement of the phototoxic effects.

Animals↗
PubMed2002

Photophysical, photochemical and antibacterial photosensitizing properties of a novel octacationic Zn(II)-phthalocyanine.

A novel Zn(II)-phthalocyanine (1). peripherally substituted with four bis(N,N,N-trimethyl)amino-2-propyloxy groups prepared by chemical synthesis is shown to be an efficient photodynamic sensitizer with a quantum yield of 0.6 for singlet oxygen generation in neat water, which is reduced to about 0.3 in phosphate-buffered saline. The physicochemical properties of 1 in both the ground and the electronically excited states strongly depend on the nature of the medium; in particular, aggregation of 1 was favoured by polar media of high ionic strength. Compound 1 exhibited an appreciable affinity for a typical Gram-positive bacterium (Staphylococcus aureus) and a typical Gram-negative bacterium (Escherichia coli). Both bacterial strains were extensively inactivated upon 5 min-irradiation with 675 nm light in the presence of 1 microM photosensitizer, even though the binding of 1 to the two bacterial cells appears to occur according to different pathways. In particular, E. coli cells underwent initial photodamage at the level of specific proteins in the outer wall, thus promoting the penetration of the photosensitizer to the cytoplasmic membrane where some enzymes critical for cell survival were inactivated.

Anti-Bacterial Agents↗
PubMed2002

Approaches to selectivity in the Zn(II)-phthalocyanine-photosensitized inactivation of wild-type and antibiotic-resistant Staphylococcus aureus.

A number of Zn(II)- phthalocyanines bearing peripheral substituents of cationic nature due to the presence of quaternarized anilinium or ammonium groups were shown to be efficient photoantimicrobial agents: a 4-5 log decrease in the survival of both wild-type or methicillin-resistant Staphylococcus aureus was obtained upon short irradiation times in the presence of phthalocyanine concentrations as low as 0.1 microM. A careful selection of the experimental protocol, and in particular the use of short (5 min) incubation times and mild irradiation parameters, allowed one to achieve a high selectivity of S. aureus photoinactivation as compared with important constituents of potential host tissues, such as human fibroblasts and keratinocytes. The efficiency and selectivity of the photoprocess were not affected by the presence of 5% human serum.

Anti-Bacterial Agents↗
PubMed2002

Photophysical properties and antibacterial activity of meso-substituted cationic porphyrins.

A series of derivatives of 5,10,15,20-tetrakis-(4-N-methylpyridyl)-porphine, where one N-methyl group was replaced by a hydrocarbon chain ranging from C6 to C22, were characterized for their photophysical and photosensitizing properties. The absorption and fluorescence features of the various compounds in neutral aqueous solutions were typical of largely monomeric porphyrins, with the exception of the C22 derivative, which appeared to be extensively aggregated. This was confirmed by the very low triplet quantum yield and lifetime of the C22 derivative as compared with 0.2-0.7 quantum yields and 88-167 micros lifetimes for the other porphyrins. The photophysical properties and photosensitizing activity toward N-acetyl-L-tryptophanamide of the C22 porphyrin became comparable to those typical of the other derivatives in 2% aqueous sodium dodecyl sulfate, where the C22 compound is fully monomerized. All the porphyrin derivatives exhibited at micromolar concentrations photoinactivation activity against both Staphylococcus aureus and Escherichia coli, even though the gram-negative bacteria were markedly less photosensitive. The photosensitizing efficiency was influenced by (1) the amount of cell-bound porphyrin, which increased with increasing length of the hydrocarbon chain; and (2) the tendency to undergo partial aggregation in the cell, which seems to be especially important for the C22 derivative.

Anti-Bacterial Agents↗
PubMedDate not supplied

Radiation therapy combined with photofrin or 5-ALA: effect on Lewis sarcoma tumor lines implanted in mice. Preliminary results.

AIMS AND BACKGROUND: Ionizing irradiation is a well-established therapeutic modality for cancer. Photodynamic therapy (PDT), especially with 5-ALA and Photofrin, is highly effective in some tumor types. Chemical modifiers, so-called radiosensitizers, are used in order to increase the efficacy of radiotherapy. Most of the known and routinely used radiosensitizers are not tumor selective, so that the normal tissue reaction toxicity is also increased. In the present study we investigated whether a porphyrin derivative that is currently used as a tumor-photosensitizing agent in photodynamic therapy (PDT) may also act as a tumor-specific radiosensitizer. MATERIALS AND METHODS: For our investigation we used Balb/c mice implanted with Lewis sarcoma and irradiated with 3 Gy combined with injection of 5-ALA or Photofrin at various concentrations before irradiation. RESULTS: 5-ALA had no effect as a radiosensitizer at any of the concentrations examined. Photofrin at a concentration of 5 mg/kg proved to be a chemical modifier of ionizing radiation, delaying tumor growth and reducing the overall tumor volume by about 50% after six days. CONCLUSION: Photofrin has marked efficacy as a radiosensitizer and can be used in the future as a selective tumor radiosensitizer.

Aminolevulinic Acid↗