RESUMEN
Nanomaterials with intrinsic enzyme-like characteristics exhibit their great potentials as alternatives to natural enzymes. Among various enzymes, the finding of substitutes of DNA photolyases, a family of photoenzymes for repairing the ultraviolet (UV)-induced DNA damage by forming cyclobutane pyrimidine dimers (CPDs) between two adjacent thymines in a DNA strand, is still unsuccessful. CPDs raise significant health concerns in various skin diseases. Essentially, DNA photolyases selectively split dimers into monomers by photoelectrons under visible-light irradiation, and this is a photocatalytic process. However, the majority of semiconductors are unprosperous due to the accompanied photogenerated reactive oxygen species (ROS), which decompose CPDs into fragments and thereby lead to a nonselective photocatalysis. Fortunately, CeO2 as a semiconductor might deliver the selectively photocatalytic repair of UV-induced DNA damages, where the photoelectrons are used for the CPD cleavage, and the photogenerated ROS are locally suppressed for its antioxidant nature. Herein, we reported the defective porous CeO2 delivered the photolyase-like activity by enhancing visible-light absorption, enabling the effective interaction between CPDs and catalysts, and subsequently triggering the selective photocleavage of CPDs into monomers. Further, in vitro cellular and in vivo animal evaluations illustrated its high potentials as alternatives to DNA photolyases.
Asunto(s)
Cerio/química , Desoxirribodipirimidina Fotoliasa/química , Nanoestructuras/química , Dímeros de Pirimidina/química , Animales , Materiales Biomiméticos/química , Catálisis , Línea Celular , Humanos , Ratones , Fotólisis , Porosidad , Rayos Ultravioleta/efectos adversosRESUMEN
Lactic acid (LA) is a powerful molecule as the metabolic driver in tumor microenvironments (TMEs). Inspired by its high intratumoral level (5-20 µmol g-1 ), a novel treatment paradigm via the cascade release of H2 O2 and ·OH from the LA generated by tumor metabolism is developed for catalytic and pH-dependent selective tumor chemotherapy. By utilizing the acidity and overexpression of LA within the TME, the constructed lactate oxidase (LOD)-immobilized Ce-benzenetricarboxylic acid (Ce-BTC) metal organic framework enables the intratumoral generation of ·OH via a cascade reaction: 1) the in situ catalytic release of H2 O2 from LA by LOD, and 2) the catalytic production of ·OH from H2 O2 by Ce-BTC with peroxidase-like activity. Highly toxic ·OH effectively induces tumor apoptosis/death. A new strategy for selective tumor chemotherapy is provided herein.
Asunto(s)
Ácido Láctico/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Catálisis , Muerte Celular , Cerio/química , Enzimas Inmovilizadas/metabolismo , Células Hep G2 , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , Oxigenasas de Función Mixta/metabolismo , Ácidos Tricarboxílicos/químicaRESUMEN
Nanoceria with phosphatase-like behavior shows its great potential for many important biological applications through a catalytic dephosphorylation process. Herein, we synthesize a series of porous nanorods of ceria (PN-CeO2) with the controllable surface Ce3+ fractions modulated by thermal annealing, understanding the correlations between their surface properties and reactivity for the dephosphorylation of p-nitrophenyl phosphate ( p-NPP) and investigating their catalytic performance under various interferences. Our results suggest that PN-CeO2 with abundant surface defects deliver higher catalytic activity to break down p-NPP. Most importantly, PN-CeO2 exhibited a better adaptability over a wide pH range and preserved the catalytic activity over a wide temperature range from 20 to 80 °C, if compared with natural enzymes. Moreover, PN-CeO2 delivered the high catalytic stability against various interference ions. Their great prospects for practical applications were further demonstrated by dephosphorylation of DNA.