RESUMO
Clinical applications of nanozyme-initiated chemodynamic therapy (NCDT) have been severely limited by the poor catalytic efficiency of nanozymes, insufficient endogenous hydrogen peroxide (H2 O2 ) content, and its off-target consumption. Herein, the authors developed a hollow mesoporous Mn/Zr-co-doped CeO2 tandem nanozyme (PHMZCO-AT) with regulated multi-enzymatic activities, that is, the enhancement of superoxide dismutase (SOD)-like and peroxidase (POD)-like activities and inhibition of catalase (CAT)-like activity. PHMZCO-AT as a H2 O2 homeostasis disruptor promotes H2 O2 evolution and restrains off-target elimination of H2 O2 to achieve intensive NCDT. PHMZCO-AT with SOD-like activity catalyzes endogenous superoxide anion (O2 â¢- ) into H2 O2 in the tumor region. The suppression of CAT activity and depletion of glutathione by PHMZCO-AT largely weaken the off-target decomposition of H2 O2 to H2 O. Elevated H2 O2 is then catalyzed by the downstream POD-like activity of PHMZCO-AT to generate toxic hydroxyl radicals, further inducing tumor apoptosis and death. T1 -weighted magnetic resonance imaging and X-ray computed tomography imaging are also achieved using PHMZCO-AT due to the existence of paramagnetic Mn2+ and the high X-ray attenuation ability of elemental Zr, permitting in vivo tracking of the therapeutic process. This work presents a typical paradigm to achieve intensive NCDT efficacy by regulating multi-enzymatic activities of nanozymes to perturb the H2 O2 homeostasis.
Assuntos
Cério , Neoplasias , Catálise , Humanos , Peróxido de Hidrogênio/uso terapêutico , Radical Hidroxila , Neoplasias/tratamento farmacológicoRESUMO
A simple and efficient method was used to synthesize norepinephrine-induced AuPd aerogels (AuPd-NE) with dual enzyme properties, i.e. glucose oxidase-like property, and peroxidase-like property. Thus, AuPd-NE aerogels can be considered as a tandem nanozyme with tandem enzyme-like activity. In the presence of AuPd-NE aerogels, glucose can be decomposed into gluconic acid and H2O2. Then, H2O2 will continue to decompose into ·OH and H2O. The generated ·OH will oxidize colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue products of ox-TMB. Accordingly, an enzyme-free method based on AuPd-NE aerogels was proposed for sensitive colorimetric detection of glucose. The linear range of the developed method was 30 to 250 µM, and the limit of detection was 10 µM. The method presents reliable applicability for blood glucose detection in human serum samples. This study will deepen the understanding of tandem nanozymes and then rationally design tandem nanozymes for many fascinating biomedical applications. A simple, sensitive and reliable one-pot enzyme-free colourimetric assay for glucose was developed.