RESUMEN
Photodynamic therapy is an alternative treatment for several pathologies, including cancer. This therapy uses a photosensitizer capable of producing reactive oxygen species through irradiation, promoting cellular death. A limitation of photosensitizers is their low solubility in aqueous media. Hence, developing a suitable carrier for photosensitizers for specific applications is a challenge. Cervical cancer is one of the most common cancers in women, and photodynamic therapy could be an attractive alternative therapeutic approach. In this work, we synthesized films composed of chitosan, polyvinylpyrrolidone, and liposomes containing Zn-phthalocyanine. Photophysical characterization of ZnPc incorporated into films was determined by UV-vis and fluorescence. Film properties such as swelling, mechanical properties, and water vapor permeability were performed. Finally, in vitro, photodynamic evaluation of these films was performed on HeLa cells. The results indicate that incorporating Zn-Pc-liposomes into films decreases cell viability by >95 %.
Asunto(s)
Quitosano , Compuestos Organometálicos , Fotoquimioterapia , Femenino , Humanos , Liposomas , Fármacos Fotosensibilizantes/farmacología , Células HeLa , Fotoquimioterapia/métodos , Compuestos de ZincRESUMEN
Non-tuberculous mycobacteria are a heterogeneous group of environmental bacteria and other than the well-known Mycobacterium tuberculosis complex and Mycobacterium leprae. They could cause localized or disseminated infections. Mycobacterium chelonae and Mycobacterium fortuitum are among the most clinically relevant non-tuberculous mycobacteria species. The infections treatment is complex since they are resistant to antituberculosis drugs and the biofilm formation makes them impermeable to several antibiotics. Antimicrobial photodynamic therapy (aPDT) constitutes an alternative to eliminate pathogens, principally those antimicrobials resistant. Among explored photosensitizers, phthalocyanines are considered excellent, but with a disadvantage: a lack solubility in aqueous media. Consequently, several nanocarriers have been studied in the last years. In this work, a Zn-phthalocyanine into liposomes was evaluated to photoinactivate M. fortuitum and M. chelonae. The results show a higher photodynamic activity of ZnPc into liposomes respect to solution. Furthermore, M. fortuitum was more sensible to aPDT than M. chelonae.
Asunto(s)
Infecciones por Mycobacterium no Tuberculosas , Mycobacterium chelonae , Mycobacterium tuberculosis , Antituberculosos/uso terapéutico , Humanos , Isoindoles , Liposomas , Infecciones por Mycobacterium no Tuberculosas/microbiología , Micobacterias no Tuberculosas , Compuestos Organometálicos , Fármacos Fotosensibilizantes/farmacología , Compuestos de ZincRESUMEN
Photodynamic therapy has emerged as an effective therapeutic alternative to treat oncological, cardiovascular, dermatological, infectious, and ophthalmic diseases. Photodynamic therapy combines the action of a photosensitizer with light in the presence of oxygen to generate reactive oxygen species, capable of reacting with cellular components, resulting in injury and, consequently, inducing cellular death. Phthalocyanines are considered good photosensitizers, although most of them are lipophilic, difficulting their administration for clinical use. A strategy to overcome the lack of solubility of phthalocyanines in aqueous media is to incorporate them into different delivery systems. The present review aimed to summarize the current status of the main drug delivery systems used for Zn and Al phthalocyanines and their effect in photodynamic therapy, reported in the last five years. Liposomes, polymeric micelles, polymeric nanoparticles, and goldnanoparticles constituted some of the most used carriers and were discussed in this review. The latest studies reported strongly suggest that the application of nanotechnologies as delivery systems allows an increase in photodynamic therapy efficacy and reduces side-effects associated with the phthalocyanine administration, which represents a hope for cancer treatments.
Asunto(s)
Fotoquimioterapia , Sistemas de Liberación de Medicamentos , Humanos , Indoles , Isoindoles , Micelas , Fármacos Fotosensibilizantes/uso terapéuticoRESUMEN
Photodynamic therapy (PDT) is considered a promising strategy for cancer treatment. PDT utilizes light in combination with a photosensitizer (PS) to induce several phototoxic reactions. Phthalocyanines (Pcs), a second generation of photosensitizers, have been studied in several cancer models. Among these, Pcs, have become of interest for the treatment of glioblastomas which are one of the most common and aggressive forms of tumors of the central nervous system. Due to the lipophilic nature of Pcs and their limited solubility in water, Pcs can be loaded in liposomes. In this work, we characterized liposomes of ZnPc and TAZnPc and their effectiveness to photoinactivate glioblastoma cells, was evaluated. Both Pcs show an increase in their photosensitizing activity when they were administrated in Dipalmitoylphosphatidylcholine-cholesterol liposomes compared to Pcs administrated in dimethylformamide.
Asunto(s)
Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Glioblastoma/tratamiento farmacológico , Indoles/farmacología , Liposomas/química , Compuestos Organometálicos/farmacología , Fármacos Fotosensibilizantes/farmacología , Línea Celular Tumoral , Humanos , Indoles/administración & dosificación , Indoles/química , Isoindoles , Estructura Molecular , Compuestos Organometálicos/administración & dosificación , Compuestos Organometálicos/química , Fotoquimioterapia , Fármacos Fotosensibilizantes/química , Compuestos de ZincRESUMEN
Glioblastoma multiforme is considered to be one of the most aggressive types of tumors of the central nervous system, with a poor prognosis and short survival periods of ~ one year. The current protocol for glioblastoma treatment includes the surgical excision of the primary tumor followed by radio and chemotherapy. Photodynamic therapy (PDT) is considered a promising strategy for the treatment of several types of tumors. Phthalocyanines (Pcs) are good photosensitizers (PSs) for PDT because they induce cell death in several cellular models. ZnPc (Zn(II)phthalocyanine) is a well-known Pc, extensively tested in different cells and tumor models, but its evaluation on a glioblastoma model has been poorly studied. Herein, we compare the capacity of ZnPc and one of its derivatives, Zn(II)tetraminephthalocyanine (TAZnPc), to photoinactivate glioblastoma cells (T98G, MO59, LN229 and U87-MG) in culture. We measured the cellular uptake, the toxicity in the dark and the subcellular localization of the different Pcs, as well as the clonogenic capacity of surviving cells after PDT. The mechanism of cell death induced after PDT was determined by measuring caspase 3 activation, DNA fragmentation, phosphatidylserine externalization, mitochondrial morphological changes and loss of mitochondrial membrane potential as well as lysosomal membrane integrity. Overall, ZnPc and TAZnPc present good properties to be used as PSs with photoinactivation capacity on glioblastoma cells.
Asunto(s)
Glioblastoma/tratamiento farmacológico , Indoles/toxicidad , Compuestos Organometálicos/toxicidad , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/toxicidad , Caspasa 3/metabolismo , Línea Celular Tumoral , Fragmentación del ADN , Humanos , Indoles/química , Indoles/farmacología , Isoindoles , Lisosomas/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Compuestos Organometálicos/química , Compuestos Organometálicos/farmacología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Compuestos de ZincRESUMEN
The worldwide increase in antibiotic resistance has led to search of alternatives anti-microbial therapies such as photodynamic inactivation. The aim of this paper was to evaluate the photodynamic activity in vitro of a neutral and two cationic Zn phthalocyanines. Their photokilling activity was tested on Escherichia coli ATCC 25922 and Klebsiella pneumoniae Carbapenemase (KPC)-producing. After treating bacteria with phthalocyanines, the cultures were irradiated with white light. As a result, the bacteria were inactivated in presence of cationic phthalocyanines. The photoinactivation was dependent of the irradiation time and phthalocyanine concentration. The most effective photosensitizer on KPC-producing was Zinc(II)tetramethyltetrapyridino[2,3-b:2',3'-g:2â³,3â³-l:2â´,3â´-q]porphyrazinium methylsulfate (ZnTM2,3PyPz). After irradiation using the water soluble ZnTM2,3PyPz (3µM) the viability of KPC (30min of irradiation) and E. coli (10min of irradiation) decreased ≈99.995%.