Enhanced antifungal efficacy of tebuconazole using gated pH-driven mesoporous nanoparticles

Núria Mas,1–3 Irene Galiana,3 Silvia Hurtado,† Laura Mondragón,1–3 Andrea Bernardos,1–3 Félix Sancenón,1–3 María D Marcos,1–3 Pedro Amorós,4 Nuria Abril-Utrillas,5 Ramón Martínez-Máñez,1–3 José Ramón Murguía1,3 1Centro de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Centro Mixto Universidad Politécnica de Valencia, Universidad de Valencia, Valencia, Spain; 2Departamento de Química, Universidad Politécnica de Valencia, Valencia, Spain; 3CIBER de Bioingeniería, Biomateriales y Nanomedicina, Madrid, Spain; 4Institut de Ciència del Materials (ICMUV), Universitat de València, Valencia, Spain; 5Servicio Ginecología y Obstetricia, Hospital de la Plana, Vila-real, Spain†Silvia Hurtado passed away in September 2013 Abstract: pH-sensitive gated mesoporous silica nanoparticles have been synthesized. Increased extracellular pH and internalization into living yeast cells triggered molecular gate aperture and cargo release. Proper performance of the system was demonstrated with nanodevices loaded with fluorescein or with the antifungal agent tebuconazole. Interestingly, nanodevices loaded with tebuconazole significantly enhanced tebuconazole cytotoxicity. As alterations of acidic external pH are a key parameter in the onset of fungal vaginitis, this nanodevice could improve the treatment for vaginal mycoses.Keywords: capped mesoporous nanoparticles, intracellular release, pH-responsive nanoparticles, Saccharomyces cerevisiae, tebuconazole loading