BACKGROUND: Clinically-approved anticancer photodynamic therapy (PDT) is now extensively studied for various cancer diagnoses. We focused on the treatment efficacy of topical administration of hydroxy-aluminum phthalocyanine (AlOH-PC) entrapped in liposomes against in vivo models of prostate carcinomas. MATERIALS AND METHODS: LNCaP and PC3 cells were subcutaneously injected into the right flank of athymic nude mice. Mice with grown tumours were used for in vivo efficacy studies. Firstly, we applied different doses of AlOH-PC to less aggressive LNCaP tumours to determine the effective dose. In later studies, we focused on more aggressive prostate tumours (PC3) using doses of liposomal-AlOH-PC gel formulation. Topical application of photosensitizers was followed by PDT irradiation (600-700 nm, 635 nm peak). Tumour growth was measured three times-a-week. RESULTS: Comparison of PDT of aggressive PC3 and less aggressive LNCaP prostate carcinomas showed that both tumour types are sensitive and treatable by liposomal formulation of AlOH-PC. For LNCaP tumours the efficient dose (100% experimental animals cured, n=8/8) was 4.5 mg/ml of AlOH-PC in the gel. Whereas, in the case of PC3 carcinomas, a dose of 4 mg/ml significantly postponed tumour growth, but no animals were cured (n=0/8); a sufficient curative dose (100% mice cured, n=8/8) was 6 mg/ml of AlOH-PC in the gel. CONCLUSION: Liposomal AlOH-PC gel has potential for effective PDT of prostate carcinomas.
- MeSH
- aplikace lokální MeSH
- fotochemoterapie * MeSH
- fotosenzibilizující látky aplikace a dávkování farmakologie MeSH
- hydroxid hlinitý chemie MeSH
- indoly chemie farmakologie MeSH
- lidé MeSH
- liposomy * MeSH
- molekulární struktura MeSH
- myši nahé MeSH
- myši MeSH
- nádorové buňky kultivované MeSH
- nádory prostaty farmakoterapie MeSH
- organokovové sloučeniny chemie farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Sulfonated phthalocyanines (Pcs) are cyclic tetrapyrroles that constitute a group of photosensitizers. In the presence of visible light and diatomic oxygen, Pcs produce singlet oxygen and other reactive oxygen species that have known degradation effects on lipids, proteins and/or nucleic acids. Pcs have been used successfully in the treatment of bacterial, yeast and fungal infections, but their use in the photodynamic inactivation of prions has never been reported. Here, we evaluated the photodynamic activity of the disodium salt of disulfonated hydroxyaluminium phthalocyanine (PcDS) against mouse-adapted scrapie RML prions in vitro. PcDS treatment of RML brain homogenate resulted in a time- and dose-dependent inactivation of prions. The photodynamic potential of Pcs offers a new way to inactivate prions using biodegradable compounds at room temperature and normal pressure, which could be useful for treating thermolabile materials and liquids.
- MeSH
- buněčné linie MeSH
- časové faktory MeSH
- fotochemoterapie metody MeSH
- indoly chemie farmakologie MeSH
- kyseliny sulfonové chemie farmakologie MeSH
- molekulární struktura MeSH
- mozek MeSH
- myši MeSH
- neurony MeSH
- priony účinky léků MeSH
- teplota MeSH
- tlak MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Phthalocyanines (Pcs) are promising photosensitizers for use in various branches of science and industry. In the presence of visible light and diatomic oxygen, phthalocyanines can react to produce singlet oxygen, a member of reactive oxygen species able to damage different molecules and tissues. The aim of this study was to investigate the ability of phthalocyanines to degrade natural toxins in the presence of visible light. As the representative of hardly degradable toxins, a group of cyanobacterial peptide toxins--microcystin-LR--was chosen for this study. According to our results, phthalocyanines are able to degrade 61.5% of microcystins within a 48-hour incubation (38% of microcystins was degraded after 24 h and 24% after 12 h of incubation). Although other oxidants like hydrogen peroxide or ozone are able to degrade microcystins within several hours, we assume that by optimizing the spectrum emitted by light source and by changing the absorption characteristics of Pcs, microcystins degradation by phthalocyanines could be more effective in the near future.
Photodynamic therapy (PDT) has been developed in recent years as a new modality for the treatment of various neoplastic and non-neoplastic lesions. Although the method of combining light with photosensitizers for treatment has been around for a century, further understanding has been evolved over the past decades. The method is based on the phenomenon involving the combination of photosensitizer and light. Neither drug nor light alone are effective as therapeutic agents. The antitumour effects result from direct cell damage, destruction of tumor vasculature and activation of a nonspecific immune response. The more accepted use of PDT is still restricted for ophthalmology, dermatology and treatment of some stages of esophageal, lung and urinary bladder cancer. In our experiments, the effect of phototherapy with disulfonated hydroxyaluminium phthalocyanine (Al(OH)S2Pc) and photofrin (control group) on the growth of human colorectal carcinoma on nude mice was studied. We chose colorectal carcinoma, because the Czech population has the highest incidence and it is still increasing. We try to offer a new possibility of treatment for patients with this severe disease.
- MeSH
- dihematoporfyrinether terapeutické užití MeSH
- fotochemoterapie MeSH
- fotosenzibilizující látky terapeutické užití MeSH
- HCT116 buňky MeSH
- indoly terapeutické užití MeSH
- kolorektální nádory farmakoterapie MeSH
- lidé MeSH
- myši MeSH
- organokovové sloučeniny terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
