Apoptotic body based biomimetic hybrid nanovesicles to attenuate cytokine storms for sepsis treatment.

Sepsis is a severe immune response to pathogens that is associated with high mortality rate and a paucity of efficacious treatment options. It is characterized by the hyperactivation of macrophages and the occurrence of cytokine storms. Given the anti-inflammatory properties of M2 macrophages and their derived apoptotic bodies (AB), as well as the specific uptake of these by macrophages, a novel approach was employed to combine AB with artificial liposomes to create apoptotic body based biomimetic hybrid nanovesicles (L-AB).

Platelet Activation-Induced In Situ Trapping Metastatic Tumor Cells Strategy for Post-Surgery Tumor Recurrence Immunochemotherapy.

The reasons for the high recurrence and metastasis after triple-negative breast cancer (TNBC) surgery are the potential presence of micrometastases and disseminated tumor cells in the circulation, as well as the immunosuppressive microenvironment caused by the surgery. To address these issues, this work proposed a platelets (PLTs) based hydrogel delivery system for immuno-chemotherapy, (IL-12+NP-PLT)@dAlg. To utilize the targeting ability of PLTs toward tumor cells and maintain the activity of PLTs, doxorubicin-loaded nanoparticles (NP) were attached on the surface of PTLs (NP-PLT).

CCL9/CCR1 axis-driven chemotactic nanovesicles for attenuating metastasis of SMAD4-deficient colorectal cancer by trapping TGF-.

SMAD4 deficiency in colorectal cancer (CRC) is highly correlated with liver metastasis and high mortality, yet there are few effective precision therapies available. Here, we show that CCR1-granulocytic myeloid-derived suppressor cells (G-MDSCs) are highly infiltrated in SMAD4-deficient CRC CCL15/CCR1 and CCL9/CCR1 axis in clinical specimens and mouse models, respectively. The excessive TGF-, secreted by tumor-infiltrated CCR1-G-MDSCs, suppresses the immune response of cytotoxic T lymphocytes (CTLs), thus facilitating metastasis.

Radiation-based immunogenic vaccine combined with a macrophage "checkpoint inhibitor" for boosting innate and adaptive immunity against metastatic colon cancers.

Immunogenic dying tumor cells hold promising prospects as cancer vaccines to activate systemic immunity against both primary and metastatic tumors. Especially, X-ray- induced dying tumor cells are rich in highly immunogenic tumor-associated antigens and self-generated dsDNA as potent adjuvants. However, we found that the X-ray induction process can result in the excessive exposure of phosphatidylserine in cancer vaccines, which can specifically bind with the MerTK receptor on macrophages, acting as a "checkpoint" to facilitate immune silence in the tumor microenvironment.

Colon Targeting pH-Responsive Coacervate Microdroplets for Treatment of Ulcerative Colitis.

Ulcerative colitis (UC), an immune-mediated chronic inflammatory disease, drastically impacts patients' quality of life and increases their risk of colorectal cancer worldwide. However, effective oral targeted delivery and retention of drugs in colonic lesions are still great challenges in the treatment of UC. Coacervate microdroplets, formed by liquid-liquid phase separation, are recently explored in drug delivery as the simplicity in fabrication, spontaneous enrichment on small molecules and biological macromolecules, and high drug loading capacity.

In situ neutrophil apoptosis and macrophage efferocytosis mediated by Glycyrrhiza protein nanoparticles for acute inflammation therapy.

In the progression of acute inflammation, the activation and recruitment of macrophages and neutrophils are mutually reinforcing, leading to amplified inflammatory response and severe tissue damage. Therefore, to regulate the axis of neutrophils and macrophages is essential to avoid tissue damage induced from acute inflammatory. Apoptotic neutrophils can regulate the anti-inflammatory activity of macrophages through the efferocytosis.

Engineered Biomimetic Nanovesicles Based on Neutrophils for Hierarchical Targeting Therapy of Acute Respiratory Distress Syndrome.

Acute Respiratory Distress Syndrome (ARDS) is a clinically severe respiratory disease that causes severe medical and economic burden. To improve therapeutic efficacy, effectively targeting delivery to the inflamed lungs and inflamed cells remains an ongoing challenge. Herein, we designed engineered biomimetic nanovesicles (DHA@ANeu-DDAB) by fusion of lung-targeting functional lipid, neutrophil membrane containing activated β integrins, and the therapeutic lipid, docosahexaenoic acid (DHA).

Hybrid Biomimetic Nanovesicles to Drive High Lung Biodistribution and Prevent Cytokine Storm for ARDS Treatment.

Acute respiratory distress syndrome (ARDS) has been a life threat for patients in ICUs. Vast efforts have been devoted, while no medication has proved viable, which may be ascribed to inadequate drug delivery to damaged tissues and insufficient control of lung inflammation. Given the anti-inflammatory role of M2-type macrophages, M2 macrophage-derived nanovesicles and lung-targeting liposomes are cofused to fabricate hybrid liposomes-nanovesicles (LNVs).