Regulating metalloimmunology with nanomedicine for cancer therapy

Metals are essential components of both micronutrients and macronutrients in living organisms and are involved in a variety of immune processes in the forms of free ions or protein-coupled complexes(metalloproteins).Multiple aspects of the immune system,from the structural and functional control of immune-related proteins to the cellular responses to immunotherapy,could be affected by metals.Therefore,the employment of metal for the regulation of immunity,termed as metalloimmunology,is gaining interest as a prevalent and efficacious approach to combating cancer.However,the manipulation of metalloimmunology using traditional drugs presents several challenges,including limited bioavailability,adverse effects,and a lack of targeting specificity.This review provides an overview of the latest findings in metal and metal-regulatory therapeutic agents for the treatment of cancer.Essential trace metal elements,such as iron,zinc,copper,manganese,magnesium,and calcium,as well as heavy metal drugs and their mechanisms of action,will be discussed with a particular focus on their roles in regulating the tumor-immune interplay.The latest nanotechnology employed in the administration of metal-regulatory drugs and the design concepts for tailored therapeutic interventions will be discussed.These concepts and information offer promising clinical possibilities of modulating cancer immunology by targeting metal metabolism.

Converting bacteria into autologous tumor vaccine via surface biomineralization of calcium carbonate for enhanced immunotherapy

Autologous cancer vaccine that stimulates tumor-specific immune responses for personalized immunotherapy holds great potential for tumor therapy.However,its efficacy is still suboptimal due to the immunosuppressive tumor microenvironment(ITM).Here,we report a new type of bacteria-based autologous cancer vaccine by employing calcium carbonate(CaCO_(3))biomineralized Salmonella(Sal)as an in-situ cancer vaccine producer and systematical ITM regulator.CaCO_(3) can be facilely coated on the Sal surface with calcium ionophore A23187 co-loading,and such biomineralization did not affect the bioactivities of the bacteria.Upon intratumoral accumulation,the CaCO_(3) shell was decomposed at an acidic microenvironment to atenuate tumor acidity,accompanied by the release of Sal and Ca^(2+)/A23187.Specifically,Sal served as a cancer vaccine producer by inducing cancer cells'immunogenic cell death(ICD)and promoting the gap junction formation between tumor cells and dendritic cells(DCs)to promote antigen presentation.Ca^(2+),on the other hand,was intermalized into various types of immune cells with the aid of A23187 and synergized with Sal to systematically regulate the immune system,including DCs maturation,macrophages polarization,and T cells activation.As a result,such bio-vaccine achieved remarkable effcacy against both primary and metastatic tumors by eliciting potent anti-tumor immunity with full biocompatibility.This work demonstrated the potential of bioengineered bacteria as bio-active vaccines for enhanced tumor immunotherapy.