We report a strategy to boost Fenton reaction triggered by an exogenous circularly polarized magnetic field (MF) enhance ferroptosis-like cell-death mediated immune response, as well endow responsive MRI capability using hybrid core-shell vesicles (HCSVs). HCSVs are prepared loading ascorbic acid (AA) in the core and poly(lactic-co-glycolic acid) shell incorporating iron oxide nanocubes (IONCs). MF triggers release of AA, resulting increase ferrous ions through redox between AA IONCs. A...

Transition-metal-catalyzed or metal-free azide–alkyne cycloadditions are methods to access 1,4- 1,5-disubstituted 1,2,3-triazoles. Although the copper-catalyzed cycloaddition 1,4-disubstituted products has been applied biomolecular reaction systems, complementary 1,5-regioisomers under aqueous and ambient conditions remains a challenge due limited substrate scope moisture-/air-sensitive catalysts. Herein, we report method 1,2,3-triazoles using Cp2Ni/Xantphos catalytic system. The proceeds...

In cancer immunotherapy, robust and efficient activation of cytotoxic CD8(+) T cell immune responses is a promising, but challenging task. Dendritic cells (DCs) are well-known professional antigen presenting that initiate regulate antigen-specific kill their target directly as well secrete IFN-γ, cytokine critical in tumor rejection. Here, we employed recently established protein cage nanoparticles, encapsulin (Encap), antigenic peptide nanocarriers by genetically incorporating the OT-1...

Recent studies on T follicular helper (Tfh) cells have significantly advanced our understanding of cell-dependent B cell responses. However, little is known about the early stage Tfh commitment by dendritic (DCs), particularly conventional CD8α+ and CD8α− DC subsets. We show that DCs localized at interfollicular zone play a pivotal role in induction antigen-specific upregulating expression Icosl Ox40l through non-canonical NF-κB signaling pathway. induced function as true helpers, resulting...

Radiation therapy (RT)-mediated tumor immunogenicity offers an opportunity for synergistic combination RT and immunotherapy. One of the challenges in clinic is to attain optimum efficacy immunotherapy with minimized overlapping toxicities. Here, achieve therapeutic combinational anti-programmed death ligand 1 (aPD-L1) immunotherapy, RT-responsive splintery snowflake-like Au nanocarriers (S-AuNC) were synthesized a method hierarchical bimetallic supra-nanostructures. Primary nanocrystals...

Natural killer (NK) cell-based immunotherapy has been considered a promising cancer treatment strategy with low side effects for early tumors and metastasis. However, the therapeutic efficacy is generally in established solid tumors. Ex vivo activation of NK cells exogenous cytokines often essential but ineffective to generate high doses functional treatment. Image-guided local delivery also suggested therapy. there lack noninvasive tools monitoring cells. Herein, magnetic nanocomplexes are...

Ferroptosis provides an opportunity to overcome the cancer cell therapeutic resistance and modulate immune system. Here interaction between ferroptosis of cells natural killer (NK) was investigated with a clinical grade iron oxide nanoparticle (ferumoxytol) for potential synergistic anti-cancer effect NK therapy in prostate cancer. When ferumoxytol mediated combined cells, cells' cytotoxic function increased. Observed activation also confirmed IFN-γ secretion lytic degranulation....

Herein, ferumoxytol (Fer) capped antiprogrammed cell death-ligand 1 (PD-L1) antibodies (aPD-L1) loaded ultralarge pore mesoporous silica nanoparticles (Fer-ICB-UPMSNPs) are formulated for a sequential magnetic resonance (MR) image guided local immunotherapy after cabazitaxel (Cbz) chemotherapy the treatment of prostate cancer (PC). The highly porous framework UPMSNP provides large capacity aPD-L1. Fer capping pores extends period aPD-L1 release and MR visibility UPMSNP. As-chosen Cbz prior...

Periodontal ligament stem cells (PDLSCs) from the periodontal tissue were recently identified as mesenchymal (MSCs). The capabilities of PDLSCs in or bone regeneration have been reported, but their immunomodulatory role T-cell immune responses via dendritic (DCs), known most potent antigen-presenting cell, has not studied. aim this study is to understand immunological function homogeneous human STRO-1+ CD146+ DC-mediated modulate disease process.We utilized highly purified (> 95%) and marrow...

Specific recognitions of pathogen associated molecular patterns by Toll-like receptors (TLRs) initiate dendritic cell (DC) activation, which is critical for coordinating innate and adaptive immune responses. Imidazoquinolines as small-molecule TLR7 agonists often suffer from prompt dissemination short half-life in the bloodstream, preventing their localization to corresponding effective DC activation. We postulated that covalent incorporation imidazoquinoline moieties onto surface...

Abstract A reactive oxygen species (ROS) responsive cleavable hierarchical metallic supra‐nanostructure (HMSN) is reported. HMSN structured with thin branches composed of primary gold (Au) nanocrystals and silver (Ag) nano‐linkers synthesized by a one‐pot aqueous synthesis selected ratio Au/Ag/cholate. ROS degradability tested in the presence endogenous exogeneous ROS. Significant ROS‐responsive structural deformation observed exposure hydrogen peroxide (H 2 O ) solution. The responsiveness...

Abstract Breast cancer remains as a challenging disease with high mortality in women. Increasing evidence points the importance of understanding crosstalk between breast cancers and immune cells, but little is known about effect cancer-derived factors on migratory properties dendritic cells (DCs) their consequent capability inducing T cell responses. Utilizing unique 3D microfluidic device, we here showed that (MCF-7, MDA-MB-231, MDA-MB-436 SK-BR-3)-derived soluble increase migration DCs...

Abstract Fabrication of functional nanostructures is a prominent issue in nanotechnology, because they often exhibit unique properties that are different from the individual building blocks. Protein cage nanoparticles attractive nanobuilding blocks for constructing due to their well‐defined symmetric spherical structures, polyvalent nature, and plasticity. Here, lumazine synthase protein nanoparticle genetically modified be used as template generate covalently display enzymes (β‐lactamase)...

Herein a practical strategy for augmenting immune activation in transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) is presented. Pluronic F127 (PF127) incorporated with Lipiodol (LPD) to achieve safe and effective delivery therapeutic agents during intra-arterial (IA) local delivery. Enhanced emulsion stability, IA infusion, embolic effect, safety, pharmacokinetics, tumor response Doxorubicin loaded PF127-LPD (Dox-PF127-LPD) TACE both vitro vivo preclinical VX2...

T follicular helper (Tfh) cells, a true B cell helper, have critical role in enhancing humoral immune responses. However, the initial differentiation of Tfh cells by dendritic (DCs), most potent antigen presenting has not been clearly understood, particularly knowledge two major conventional subsets, CD8α(+) DCs or CD8α(-) DCs. Here we demonstrated that localization marginal zone (MZ) bridging channels is closely associated with induction CXCR5(+)CCR7(low) cells. We also showed source IL-6...

Immune checkpoint inhibitor (ICI) cancer immunotherapies are becoming one of the standard therapies for patients. However, ICI immunotherapy's overall response rate is still moderate and even combinational not showing significant improvement in therapeutic outcomes. Only a subset patients responds to therapy due resistance ignorance immunotherapy. Following immune-related adverse events (irAEs) also limiting whole regimens. New approaches that can increase immunotherapeutic efficacy reduce...

Rodent HCC rat models provide advantages for interventional oncology (IO) based immunotherapy research compared to other established larger animal or mice models. Rapid and predictable tumor growth affordable costs permit the formation of a compelling preclinical model investigating novel IO catheter-directed therapies local ablation therapies. Among orthotopic models, N1-S1 has been involved in many cases. Suboptimal induction rates potential spontaneous regression during implantation...

Abstract Targeted cancer therapies have been extensively tested with the purpose to selectively suppress tumor growth and avoid harming healthy tissue. However, failure escape endosomes upon receptor‐mediated endocytosis is a major obstacle limiting efficacy of targeted therapeutics. Here, novel target‐switchable intracellular toxin delivery systems (TiTDS) are presented which use catalytic translocation domain diphtheria (dtA‐T) as an platform affibody molecules targeting human epidermal...

In preclinical studies, we investigated a novel mechanism of in situ vaccination lymphoma. Radiation therapy (RT) can induce abscopal responses lymphoma models, but this has not translated into clinical efficacy. We hypothesized that immune stimulation with cytosine guanine dinucleotide (CpG) deoxynucleotides could enhance effects induced by RT or photothermal (PTT), which been shown to have an stimulatory effect solid tumors studied designed branched gold nanoparticle (NP) platform carry...

Ferumoxytol capped anti PD-L1 antibodies (aPD-L1) loaded ultra-large pore mesoporous silica nanoparticles (Fer-ICB-UPMSNPs) are delivered with image guidance after cabazitaxel (Cbz) chemotherapy for the treatment of prostate cancer. Sustained release ICB from UPMSNP inhibits immunosuppressive tumor microenvironment and activates specific dendritic cells (DC). Activated antigen presenting educate naïve T cells, cytotoxic infiltrated to regression. More details can be found in article number...