Designing macrophage membrane-engineered ruthenium/selenium nanoparticles to block bone metastasis of breast cancer

Bone metastasis along with osteolysis is a common complication of advanced breast cancer,which directly destroys bone function and becomes one of the major causes of cancer-related mortality.It is crucial to develop a new strategy to achieve effective cancer therapy and inhibition of osteolytic bone metastasis.Metal ruthenium(Ru)complexes exhibit therapeutic potential in cancer chemotherapy.However,the clinical applications of Ru complexes were limited by poor bioavailability,lacking targeting,nonspecific distribution.Therefore,in this study,engineering of cell membrane biomimetic modification was used to construct a highly biocompatible nanoplatform with carrying Ru metal complex of RuPOP and Se nanoparticles(SeNPs).Strikingly,the obtained RPSR nanoparticles can efficiently inhibit the proliferation,invasion and migration of breast cancer cells(MDA-MB-231 cells)in vitro.More importantly,RPSR nanoparticles can induce cycle arrest,apoptosis by generating excessive intracellular(reactive oxygen species,ROS)to disrupt the normal redox balance and induce DNA damage in tumor cells.Furthermore,RPSR nanoparticles can also reshape bone microenvironment by regulating selenoproteins to inhibit osteoclasts and avoid osteolytic bone metastasis induced by tumor development.Taken together,this study not only provides an effective cell membrane biomimetic strategy to enhance the shortcomings of metal complexes,but also demonstrates potential clinical significance for the combined treatment of anti-cancer and bone metastasis inhibition.

Technical advances in NK cell-based cellular immunotherapy

Natural killer(NK)cells represent a promising future for tumor immunotherapy because of their unique biological functions and characteristics.This review focuses on technical advances in NK cell-based cellular immunotherapy and summarizes the developments of recent years in cell sources,genetic modification,manufacturing systems,clinical programs,and outcomes.Future prospects and challenges in NK cell immunotherapy are also discussed,including off-the-shelf NK cell exploitation,automatic and closed manufacturing systems,cryopreservation,and therapies involving regulatory checkpoints.

Spatial distribution of IL4 controls iNKT cell-DC crosstalk in tumors

The spatiotemporal distribution of cytokines orchestrates immune responses in vivo,yet the underlying mechanisms remain to be explored.We showed here that the spatial distribution of interleukin-4(IL4)in invariant natural killer T(iNKT)cells regulated crosstalk between iNKT cells and dendritic cells(DCs)and controlled iNKT cell-mediated T-helper type 1(Th1)responses.The persistent polarization of IL4 induced by strong lipid antigens,that is,α-galactosylceramide(αGC),caused IL4 accumulation at the immunological synapse(IS),which promoted the activation of the IL4R-STAT6(signal transducer and activator of transcription 6)pathway and production of IL12 in DCs,which enhanced interferon-γ(IFNγ)production in iNKT cells.Conversely,the nonpolarized secretion of IL4 induced by Th2 lipid antigens with a short or unsaturated chain was incapable of enhancing this iNKT cell-DC crosstalk and thus shifted the immune response to a Th2-type response.The nonpolarized secretion of IL4 in response to Th2 lipid antigens was caused by the degradation of Cdc42 in iNKT cells.Moreover,reduced Cdc42 expression was observed in tumorinfiltrating iNKT cells,which impaired IL4 polarization and disturbed iNKT cell-DC crosstalk in tumors.