Photoactivatable Cell-Surface DNAzyme Sensor for Real-Time Monitoring of the Metal Ion-Induced AβAggregation

Precisely monitoring the distribution and local fluctuation of metal ions,which play vital roles in many physiological and pathological processes,contributes largely to the study of metal ion-induced pathogenesis.However,current reactive fluorescent sensors can hardly realize the monitoring of metal ions in situ due to the premature activation and aimless dispersion of the sensors,which hinder their applications in biological samples.Herein,we report a photoactivatable cell-surface DNAzyme sensor to monitor metal ions in the microenvironment of living cells or tissues with high spatial resolution and temporal control.The sensor can efficiently anchor to the cell membrane through amphipathic interaction,and the activity of the sensor can be restored after the irradiation by light,which avoids false positive signals from the reaction with metal cofactors during delivery.First,the properties of the sensor were investigated either in buffer or on amodel cell surface,inwhich the sensor responded to Zn2+with superior temporal and spatial resolution under light activation.Then,the sensor was applied tomonitor the dynamic changes ofmetal ions during the formation of Aβaggregates in the cellular microenvironment of brain cells and brain tissues.This strategy provides a potential tool to understand the roles ofmetal ions in the progression of diseases,such as Alzheimer’s disease.

Highly-efficient quantitative fluorescence resonance energy transfer measurements based on deep learning

Intensity-based quantitative fluorescence resonance energy transfer(FRET)is a technique to measure the distance of molecules in scale of a few nanometers which is far beyond optical diffraction limit.This widely used technique needs complicated experimental process and manual image analyses to obtain precise results,which take a long time and restrict the application of quantitative FRET especially in living cells.In this paper,a simplified and automatic quanti-tative FRET(saqFRET)method with high efficiency is presented.In saqFRET,photo-activatable acceptor PA-mCherry and optimized excitation wavelength of donor enhanced green fluorescent protein(EGFP)are used to simplify FRET crosstalk elimination.Traditional manual image analyses are time consuming when the dataset is large.The proposed automatic image analyses based on deep learning can analyze 100 samples within 30 s and demonstrate the same precision as manual image analyses.

Current Status for Oral Platinum (IV) Anticancer Drug Development

Platinum-based chemotherapeutic drugs such as cisplatin, carboplatin and oxaliplatin are widely applied for the treatment of various types of tumors. However, poor solubility, serious side effects, and more importantly, the intrinsic and acquired resistance limit their clinical applications. These factors motivate scientists to design and synthesize novel and more potent analogues lacking disadvantages of clinical platinum drugs. Platinum (IV) complexes are one of representatives. In this review, we summarized the investigations undertaken into Platinum (IV) antitumor compounds since Rosenberg first noted their antitumor activity. The synthesis method and mechanism of action of Platinum (IV) complexes are outlined, as well as their chemical and pharmacological properties. Recent advances in Platinum (IV) anticancer agents that have been in clinical trials and photoactivatable Platinum (IV) complexes are also summarized, and the purpose here is to provide insight into the requirements for the antitumor activity of Platinum (IV) complexes and a basis for progressing in a new platinum compound.