RESUMEN
The clinical translation of photosensitizers based on ruthenium(II) polypyridyl complexes (RPCs) in photodynamic therapy of cancer faces several challenges. To address these limitations, we conducted an investigation to assess the potential of a cubosome formulation stabilized in water against coalescence utilizing a polyphosphoester analog of Pluronic F127 as a stabilizer and loaded with newly synthesized RPC-based photosensitizer [Ru(dppn)2(bpy-morph)](PF6)2 (bpy-morph = 2,2'-bipyridine-4,4'-diylbis(morpholinomethanone)), PS-Ru. The photophysical characterization of PS-Ru revealed its robust capacity to induce the formation of singlet oxygen (1O2). Furthermore, the physicochemical analysis of the PS-Ru-loaded cubosomes dispersion demonstrated that the encapsulation of the photosensitizer within the nanoparticles did not disrupt the three-dimensional arrangement of the lipid bilayer. The biological tests showed that PS-Ru-loaded cubosomes exhibited significant phototoxic activity when exposed to the light source, in stark contrast to empty cubosomes and to the same formulation without irradiation. This promising outcome suggests the potential of the formulation in overcoming the drawbacks associated with the clinical use of RPCs in photodynamic therapy for anticancer treatments.
Asunto(s)
Neoplasias Pulmonares , Fotoquimioterapia , Fármacos Fotosensibilizantes , Rutenio , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/síntesis química , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Humanos , Rutenio/química , Rutenio/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/síntesis química , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/patología , Antineoplásicos/química , Antineoplásicos/farmacología , Tamaño de la Partícula , Oxígeno Singlete/metabolismo , Oxígeno Singlete/química , Nanopartículas/química , Supervivencia Celular/efectos de los fármacos , Poloxámero/química , Ensayos de Selección de Medicamentos Antitumorales , Propiedades de Superficie , Células A549RESUMEN
HALT (The Headphone and Loudspeaker Test) Part II is a continuation of HALT Part I. The main goals of this study (HALT Part II) were (a) to develop screening tests and strategies to discriminate headphones from loudspeakers, (b) to come up with a methodological approach to combine more than two screening tests, and (c) to estimate data quality and required sample sizes for the application of screening tests. Screening Tests A and B were developed based on psychoacoustic effects. In a first laboratory study (N = 40), the two tests were evaluated with four different playback devices (circumaural and intra-aural headphones; external and laptop loudspeakers). In a final step, the two screening tests A and B and a previously established test C were validated in an Internet-based study (N = 211). Test B showed the best single-test performance (sensitivity = 80.0%, specificity = 83.2%, AUC = .844). Following an epidemiological approach, the headphone prevalence (17.67%) was determined to calculate positive and negative predictive values. For a user-oriented, parameter-based selection of suitable screening tests and the simple application of screening strategies, an online tool was programmed. HALT Part II is assumed to be a reliable procedure for planning and executing screenings to detect headphone and loudspeaker playback. Our methodological approach can be used as a generic technique for optimizing the application of any screening tests in psychological research. HALT Part I and II complement each other to form a comprehensive overall concept to control for playback conditions in Internet experiments.