Engineering of dendritic cell bispecific extracellular vesicles for tumor-targeting immunotherapy.

Advances in the development of therapeutic extracellular vesicles (EVs) for cancer immunotherapy have allowed them to emerge as an alternative to cell therapy. In this proof-of-concept work, we develop bispecific EVs (BsEVs) by genetically engineering EV-producing dendritic cells (DCs) with aCD19 scFv and PD1 for targeting tumor antigens and blocking immune checkpoint proteins simultaneously. We find that these bispecific EVs (EVs-PD1-aCD19) have an impressive ability to accumulate in huCD19-expressing solid tumors following intravenous injection.

Genetically Engineered Hematopoietic Stem Cells Deliver TGF-β Inhibitor to Enhance Bone Metastases Immunotherapy.

Owing to the immune microenvironment of bones and low selectivity of the drug, patients with bone metastases often respond poorly to immunotherapy. In this study, programmed cell death protein 1 (PD1)-expressing hematopoietic stem cells (HSCs) are genetically engineered for bone-targeted delivery of the transforming growth factor beta (TGF-β) small-molecule inhibitor SB-505124 (SB@HSCs-PD-1). Intriguingly, compared to anti-PD-L1 monoclonal antibodies, as "living drugs", HSCs-PD-1 not only show great targeting ability to the bone marrow, but are also able to reduplicate themselves within the bone marrow niche and continuously express PD-1 molecules.

Yeast-derived nanoparticles remodel the immunosuppressive microenvironment in tumor and tumor-draining lymph nodes to suppress tumor growth.

Microbe-based cancer immunotherapy has recently emerged as a hot topic for cancer treatment. However, serious limitations remain including infection associated side-effect and unsatisfactory outcomes in clinic trials. Here, we fabricate different sizes of nano-formulations derived from yeast cell wall (YCW NPs) by differential centrifugation.

Bioadhesive injectable hydrogel with phenolic carbon quantum dot supported Pd single atom nanozymes as a localized immunomodulation niche for cancer catalytic immunotherapy.

Immunotherapy is a powerful way to treat cancer, however, systemic treatment-associated adverse effects remain a major concern. In this study, a bioadhesive injectable hydrogel is developed to provide localized immune niches for tumor microenvironment immunomodulation and cancer catalytic immunotherapy. First, a phenolic single atom nanozyme (SAN) was developed by in situ synthesis of Pd single atom on catechol-grafted carbon-quantum-dot (DA-CQD@Pd) templates.

Injectable Erythrocyte Gel Loaded with Bulleyaconitine A for the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease with clinical manifestations including joint cartilage, synovitis, and bone damage. Here we developed an injectable erythrocyte gel loaded with Bulleyaconitine A (BLA) for the treatment of RA and demonstrated its anti-inflammatory effects and . experiments showed that BLA could effectively down-regulate the expression of pro-inflammatory factor in activated macrophages through the nuclear factor-κB (NF-κB) pathway.

Degradation-resistant implanted biomaterials establish an immunosuppressive microenvironment that induces T cell exhaustion by recruiting myeloid cells.

Implanted biomaterials have transformed healthcare and the treatment of injury and disease, but their influence on the local immune landscape remains unclear. Here we discovered that degradation-resistant titanium-based implants establish an immunosuppressive microenvironment by recruiting myeloid cells, including monocytes, macrophages, neutrophils, and myeloid-lineage dendritic cells. Unlike normal tissues, the tissues nearby implants exhibit an chronic inflamed and immunosuppressive status characterised by myeloid-rich, T cell-exhaustion gene signature by single-cell RNA sequencing.

Mesenchymal Stem Cell-Derived Extracellular Vesicles with High PD-L1 Expression for Autoimmune Diseases Treatment.

Autoimmune diseases are the third most common disease influencing the quality of life of many patients. Here, a programmed cell death-ligand 1 + (PD-L1) mesenchymal stem cell (MSC) derived extracellular vesicles (MSC-sEVs-PD-L1) using lentivirus-mediated gene transfection technology is developed for reconfiguration of the local immune microenvironment of affected tissue in autoimmune diseases. MSC-sEVs-PD-L1 exhibits an impressive ability to regulate various activated immune cells to an immunosuppressed state in vitro.

3D Printing Scaffold Vaccine for Antitumor Immunity.

Cancer vaccine platform has attracted great interest in the field of cancer immunotherapy. Here, 3D printed scaffolds loaded with immunoregulators are developed for enhanced cancer immunotherapy. The rapid manufacturing and precise molding based on 3D printing can realize the mass manufacturing of cancer vaccines and personalized design.

Targeted delivery of dexamethasone in acute pneumonia.

Pneumonia has contributed to significant mortality owing to the irreversible injury to the lungs and severe inflammation of the tissue. Dexamethasone (DEX) is regarded as an effective drug to relieve the level of pneumonia, while the adverse effect of which is non-negligible. Here, we developed a targeted delivery strategy based on platelet-derived extracellular vesicles (PEVs), which are naturally occurring nanoparticles released by platelets, for DEX delivery in acute pneumonia, aiming to reduce the side effects and improve the therapeutic efficacy.

Implantable blood clot loaded with BMP-2 for regulation of osteoimmunology and enhancement of bone repair.

The treatment of large-area bone defects still faces many difficulties and challenges. Here, we developed a blood clot delivery platform loaded with BMP-2 protein (BMP-2@BC) for enhanced bone regeneration. Blood clot gel platform as natural biomaterials can be engineered from autologous blood.

Immunosuppressive Nanoparticles for Management of Immune-Related Adverse Events in Liver.

Immune checkpoint blockade (ICB) therapy has been considered as an effective way to boost immune cells to recognize and attack tumors. However, side effects known as immune-related adverse events (irAEs) should be carefully managed. Here, we engineer immunosuppressive nanoparticles by coating PD-L1 overexpressed mesenchymal stem cells (MSCs) plasma membrane on poly lactic--glycolic acid nanoparticles (MSC-PD-L1 NPs) for managing and reducing irAEs induced by immune checkpoint inhibitors.

Physiologically triggered injectable red blood cell-based gel for tumor photoablation and enhanced cancer immunotherapy.

Hydrogels are widely used for drug delivery and tissue engineering. Here we developed a simple injectable red blood cells (RBCs)-based gel for cancer photo-immunotherapy. We find that subcutaneous injected homologous RBCs could form hydrogel-like composition in mice, due to the infiltrated platelets and thrombin under physiological environment.

An implantable blood clot-based immune niche for enhanced cancer vaccination.

Cancer immunotherapy using cancer vaccines has shown great potential in the prevention and treatment of cancer. Here, we report an implantable autologous blood clot scaffold for enhanced cancer vaccination. It comprises a gel-like fibrin network formed by coagulation of blood to trap a large number of red blood cells.