Multifunctional Co‐Delivery Systems with Downregulation of the Novel Target PIM1 in Macrophages to Ameliorate TF‐Mediated Coagulopathy in Sepsis

Small, Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

Disordered coagulation is an independent risk factor for mortality in patients with sepsis and currently lacks effective therapeutic strategies. In this study, PIM1, a novel target predominantly expressed macrophages during sepsis, investigated by bioinformatics analysis clinical evaluation compared healthy individuals. The regulatory mechanism which PIM1 promotes the release of tissue factors (TF) from modulating phosphorylation levels mTOR through AKT MAPK signaling pathways demonstrated both vitro vivo. Based on these findings, multifunctional co-delivery system based mesoporous polydopamine (MPDA) nanoparticles (NPs) coated cationic polyethyleneimine (PEI) macrophage-targeting glucomannan (GM) (MPDA@PEI@GM NPs) proposed inhibitors SMI-4a small interfering RNA (siPIM1) to downregulate expression improve sepsis-induced coagulopathy. MPDA@SMI-4a@PEI/siPIM1@GM demonstrates negligible cytotoxicity, excellent efficiency, prolonged blood circulation, significantly downregulated expression. Notably, treatment improves survival rates septic mice ameliorating disordered alleviating lung injury. Bioinformatic research-guided systems TF-mediated coagulopathy alleviate acute injury, marking significant advancement development antisepsis therapies.

Язык: Английский

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Live bacterial chemistry in biomedicine

Chem, Год журнала: 2025, Номер unknown, С. 102436 - 102436

Опубликована: Апрель 1, 2025

Язык: Английский

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Ultrasound-Energized OX40L-Expressing Biohybrid for Multidimensional Mobilization of Sustained T Cell-Mediated Antitumor Immunity and Potent Sono-Immunotherapy

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Апрель 9, 2025

Harnessing immunostimulation to reinvigorate antitumor effector immune cells represents a promising strategy for tumor eradication. However, achieving durable clinical outcomes necessitates multidimensional activation sustain robust responses. Here, we present an ultrasound-empowered living biohybrid that strategically mobilizes T-cell-mediated immunity potent sono-immunotherapy. Through synthetic biology, engineer bacteria express fusion protein encoding the costimulatory OX40 ligand (OX40L), and further functionalize them with high-performance polymer sonosensitizer tethered via reactive oxygen species-cleavable linker. Upon ultrasound irradiation, sono-activated nanocargoes detach from bacterial surface, facilitating cellular entry exposing immune-stimulating OX40L. The sonodynamic effects, coupled native immunogenicity of bacteria, promotes tumor-associated antigen release, fosters proinflammatory microenvironment, drives dendritic cell maturation, thereby priming cytotoxic T-cell activation. OX40L expressed by engineered amplifies sustains activity, orchestrating response. This cascade-amplified effectively suppresses growth, induces long-lasting memory, provides protection against metastasis recurrence, significantly enhancing survival outcomes. By integrating ultrasound-energized nanoadjuvants boosters, this hybrid biotherapeutic platform offers versatile powerful activation, advancing frontier cancer

Язык: Английский

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Combating cancer immunotherapy resistance: a nano‐medicine perspective

Cancer Communications, Год журнала: 2025, Номер unknown

Опубликована: Апрель 10, 2025

Abstract Cancer immunotherapy offers renewed hope for treating this disease. However, cancer cells possess inherent mechanisms that enable them to circumvent each stage of the immune cycle, thereby evading anti‐cancer immunity and leading resistance. Various functionalized nanoparticles (NPs), modified with cationic lipids, pH‐sensitive compounds, or photosensitizers, exhibit unique physicochemical properties facilitate targeted delivery therapeutic agents tumor microenvironment (TME). These NPs are engineered modify activity. The crucial signal transduction pathways by which counteract resistance outlined, including enhancing antigen presentation, boosting activation infiltration tumor‐specific cells, inducing immunogenic cell death, counteracting immunosuppressive conditions in TME. Additionally, review summarizes current clinical trials involving NP‐based immunotherapy. Ultimately, it highlights potential nanotechnology advance

Язык: Английский

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Surface-Functionalized Bacteria: Frontier Explorations in Next-Generation Live Biotherapeutics

Biomaterials, Год журнала: 2024, Номер 317, С. 123029 - 123029

Опубликована: Дек. 15, 2024

Язык: Английский

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