Peptide-assembled siRNA nanomicelles confine MnOx-loaded silicages for synergistic chemical and gene-regulated cancer therapy

Chemodynamic therapy(CDT) is a promising therapeutic approach for in situ cancer treatment, but it is still hindered by inefficient single-modality treatment and the weak targeted delivery of reagents into mitochondria(the main site of intracellular ROS production). Herein, to obtain a multimodal strategy,peptide-assembled si RNA nanomicelles were prepared to confine ultrasmall MnOxin small silica cages(silicages), which is convenient for synergistic chemical and gene-regulated cancer therapy. Given the free energy and versatility of small silicages, as well as the excellent Fenton-like activity of ultrasmall MnOx,MnOx-inside-loaded silicages(10 nm) were prepared for CDT delivery to mitochondria. Subsequently, to obtain a synergistic CDT and gene silencing treatment, the peptide-mediated assembly of si RNA and MnOx-loaded silicages were employed to obtain silicage@MnOx-si RNA nanomicelles(SMS NMs). After multiple modifications, sequential cancer cell-targeted delivery, GSH-controlled reagent release of si RNA and mitochondria-targeted delivery of MnOx-loaded silicages were successfully achieved. Finally, by both in vitro and in vivo experiments, SMS NMs were confirmed to be effective for synergistic chemical and gene-regulated cancer therapy. Our findings expand the applications of silicages and initiate the development of multimodal CDT.

功能化二氧化硅纳米材料在肿瘤治疗领域的应用

纳米材料(如脂质体、聚合物胶束、树枝状聚合物)基于其良好的物理化学特性,在药物递送、成像诊断等肿瘤诊疗领域拥有巨大的应用前景.其中,介孔二氧化硅纳米材料(mesoporous silica nanomaterials,MSNs)具有独特的孔径结构、较大的比表面积,并且其粒径大小、形貌结构易于调控,同时结合多种修饰手段,在生物医学领域引起了广泛的关注.MSNs材料功能化修饰后,可作为化学药物、基因、核酸、多肽、蛋白酶等治疗药物载体,在内、外源性刺激触发下,对肿瘤部位进行特异性靶向识别和可控性药物释放,使得肿瘤诊疗一体化成为可能.本文在对MSNs材料独特的物理化学特性进行介绍的基础上,综述了其在现代生物医学中的发展趋势,并展望了其在临床应用中的巨大潜力.

Accelerated plasma degradation of organic pollutants in milliseconds and examinations by mass spectrometry

The rapid degradation of organic pollutants,process monitoring and online controlling to obtain advanced products and decreased by-products are great and challenging tasks in environmental treatments.Herein,an accelerated plasma degradation in milliseconds was achieved by combining electrospray-based acceleration and plasma-based degradation.Taking the degradation of chloroaniline as an example,97%of the degradation can be achieved in milliseconds.The velocity distribution of droplets was determined to be 40-50 m/s after being degraded for 0.30 ms,which exhibited different degradation behaviors in different milliseconds.Simultaneously,by virtue of the real-time and on-line detection ability of ambient mass spectrometry,intermediates,by-products and advanced products were monitored.Therefore,degradation mechanisms for different degradation times were proposed,which would provide theoretical guidance on obtaining efficient and green degradation.The fabrication,examining and understanding of accelerated plasma degradation not only enlarged application of accelerated reactions,but also promoted green and efficient degradation for environmental treatments.

Fluorescence resonance energy transfer-based nanomaterials for the sensing in biological systems

The applications of fluorescence resonance energy transfer(FRET)are coming to be one of the simplest and most accessible strategy with super-resolved optical measurements.Meanwhile,nanomaterials have become ideal for constructing FRET-based system,due to their unique advantages of tunable emission,broad absorption,and long fluorescence(FL)lifetime.The limitations of traditional FRET-based detections,such as the intrinsic FL,auto-FL,as well as the short FL lifetime,could be overcome with nanomaterials.Consequently,numbers of FRET-based nanomaterials have been constructed for precise,sensitive and selective detections in biological systems.They could act as both energy donors and/or acceptors in the optical energy transfer process for biological detections.Some other nanomaterials would not participate in the energy transfer process,but act as the excellent matrix for modifications.The review will be roughly classified into nanomaterial-involved and uninvolved ones.Different detection targets,such as nucleic acids,pathogenic microorganisms,proteins,heavy metal ions,and other applications will be reviewed.Finally,the other biological applications,including environmental evaluation and mechanism studies would also be summarized.