Genetically engineered nanomodulators elicit potent immunity against cancer stem cells by checkpoint blockade and hypoxia relief

Rapid development of checkpoint inhibitors has provided significant breakthroughs for cancer stem cell(CSC)therapy,while the therapeutic efficacy is restricted by hypoxia-mediated tumor immune evasion,especially hypoxia-induced CD47 overexpression in CSCs.Herein,we developed a genetically engineered CSC membrane-coated hollow manganese dioxide(hMnO_(2)@gCMs)to elicit robust antitumor immunity by blocking CD47 and alleviating hypoxia to ultimately achieve the eradication of CSCs.The hMnO_(2)core effectively alleviated tumor hypoxia by inducing decomposition of tumor endogenous H_(2)O_(2),thus suppressing the CSCs and reducing the expression of CD47.Cooperating with hypoxia relief-induced downregulation of CD47,the overexpressed SIRPαon gCM shell efficiently blocked the CD47-SIRPα“don’t eat me”pathway,synergistically eliciting robust antitumor-mediated immune responses.In a B16F10-CSC bearing melanoma mouse model,the hMnO_(2)@gCMs showed an enhanced therapeutic effect in eradicating CSCs and inhibiting tumor growth.Our work presents a simple,safe,and robust platform for CSC eradication and cancer immunotherapy.

Aggregation-induced emission:recent applications in infectious diseases

Infectious diseases are caused by various pathogenic microorganisms that break through the human immune barrier,then reproduce and mutate in human cells,thus causing invasive disease.Despite many recent scientific and technological advances in fields,such as genetics,chemistry,and protein engineering,and in the efficiency of drug research and development,the discovery and development of novel and potent anti-infectious disease agents have still lagged behind.It is often challenging to keep up with the emergence and mutation of new pathogenic microorganisms,which leads to the emergence of more resistant pathogenic microorganisms.The emergence of aggregation-induced emission(AIE)fluorogens with high luminescence yields and high reactive oxygen species(ROS)production rates provides scientists with a new strategy for the prevention and treatment of pathogenic microorganisms.Due to their advantages in terms of brightness,biocompatibility,photostability,and positive correlation,AIE fluorogens(AIEgens)have great potential in biological applications.This review presents a systemic overview of recent progress in AIEgen-based platforms for the photodynamic therapy(PDT)of infectious diseases,which has emerged as a promising noninvasive alternative to traditional antibiotics for combating the drug resistance of infectious diseases.This review is mainly divided into two parts according to the type of pathogenic microorganisms:a section on bacterial and fungal infections(e.g.,eye,skin,oral cavity,and blood infections),and a section on viral infections.The future prospects and potential clinical applications of AIEgens are also discussed in detail.In addition to motivating further interest in this field,this review is intended to promote ideas for the further exploration of AIEgens and the development of more advanced AIEgens in a broader range of biomedical and clinical applications.