Red Blood Cell-Mimic Nanocatalyst Triggering Radical Storm to Augment Cancer Immunotherapy

Red blood cells(RBCs)have recently emerged as promosing candidates for cancer treatment in terms of relieving tumor hypoxia and inducing oxidative damage against cancer cells,but they are still far from satisfactory due to their limited oxygen transport and reactive oxygen species generation rate in tumor tissue.Herein,artificial RBCs(designated FTP@RBCM)with radical storm production ability were developed for oncotherapy through multidimensional reactivity pathways of Fe-protoporphyrin-based hybrid metal-organic frameworks(FTPs,as the core),including photodynamic/chemodynamic-like,catalase-like and glutathione peroxidase-like activities.Meanwhile,owing to the advantages of long circulation abilities of RBCs provided by their cell membranes(RBCMs),FTP with a surface coated with RBCMs(FTP@RBCM)could enormously accumulate at tumor site to achieve remarkably enhanced therapeutic efficiency.Intriguingly,this ROS-mediated dynamic therapy was demonstrated to induce acute local inflammation and high immunogenic cancer death,which evoked a systemic antitumor immune response when combined with the newly identified T cell immunoglobulin and mucin-containing molecule 3(Tim-3)checkpoint blockade,leading to not only effective elimination of primary tumors but also an abscopal effect of growth suppression of distant tumors.Therefore,such RBC-mimic nanocatalysts with multidimensional catalytic capacities might provide a promising new insight into synergistic cancer treatment.

Current research status of tumor cell biomarker detection

With the annual increases in the morbidity and mortality rates of tumors,the use of biomarkers for early diagnosis and real-time monitoring of tumor cells is of great importance.Biomarkers used for tumor cell detection in body fluids include circulating tumor cells,nucleic acids,protein markers,and extracellular vesicles.Among them,circulating tumor cells,circulating tumor DNA,and exosomes have high potential for the prediction,diagnosis,and prognosis of tumor diseases due to the large amount of valuable information on tumor characteristics and evolution;in addition,in situ monitoring of telomerase and miRNA in living cells has been the topic of extensive research to understand tumor development in real time.Various techniques,such as enzyme-linked immunosorbent assays,immunoblotting,and mass spectrometry,have been widely used for the detection of these markers.Among them,the detection of tumor cell markers in body fluids based on electrochemical biosensors and fluorescence signal analysis is highly preferred because of its high sensitivity,rapid detection and portable operation.Herein,we summarize recent research progress in the detection of tumor cell biomarkers in body fluids using electrochemical and fluorescence biosensors,outline the current research status of in situ fluorescence monitoring and the analysis of tumor markers in living cells,and discuss the technical challenges for their practical clinical application to provide a reference for the development of new tumor marker detection methods.

CB1R-stabilized NLRP3 inflammasome drives antipsychotics cardiotoxicity

Long-term use of antipsychotics is a common cause of myocardial injury and even sudden cardiac deaths that often lead to drug withdrawn or discontinuation.Mechanisms underlying antipsychotics cardiotoxicity remain largely unknown.Herein we performed RNA sequencing and found that NLRP3 inflammasome-mediated pyroptosis contributed predominantly to multiple antipsychotics cardiotoxicity.Pyroptosis-based small-molecule compound screen identified cannabinoid receptor 1(CB1R)as an upstream regulator of the NLRP3 inflammasome.Mechanistically,antipsychotics competitively bond to the CB1R and led to CB1R translocation to the cytoplasm,where CB1R directly interacted with NLRP3 inflammasome via amino acid residues 177–209,rendering stabilization of the inflammasome.Knockout of Cb1r significantly alleviated antipsychotic-induced cardiomyocyte pyroptosis and cardiotoxicity.Multi-organ-based investigation revealed no additional toxicity of newer CB1R antagonists.In authentic human cases,the expression of CB1R and NLRP3 inflammasome positively correlated with antipsychotics-induced cardiotoxicity.These results suggest that CB1R is a potent regulator of the NLRP3 inflammsome-mediated pyroptosis and smallmolecule inhibitors targeting the CB1R/NLRP3 signaling represent attractive approaches to rescue cardiac side effects of antipsychotics.

Requirement and Development of Hydrogel Micromotors towards Biomedical Applications

With controllable size,biocompatibility,porosity,injectability,responsivity,diffusion time,reaction,separation,permeation,and release of molecular species,hydrogel microparticles achieve multiple advantages over bulk hydrogels for specific biomedical procedures.Moreover,so far studies mostly concentrate on local responses of hydrogels to chemical and/or external stimuli,which significantly limit the scope of their applications.Tetherless micromotors are autonomous microdevices capable of converting local chemical energy or the energy of external fields into motive forces for self-propelled or externally powered/controlled motion.If hydrogels can be integrated with micromotors,their applicability can be significantly extended and can lead to fully controllable responsive chemomechanical biomicromachines.However,to achieve these challenging goals,biocompatibility,biodegradability,and motive mechanisms of hydrogel micromotors need to be simultaneously integrated.This review summarizes recent achievements in the field of micromotors and hydrogels and proposes next steps required for the development of hydrogel micromotors,which become increasingly important for in vivo and in vitro bioapplications.