Dendritic Nanomedicine with Boronate Bonds for Augmented Chemo‐Immunotherapy via Synergistic Modulation of Tumor Immune Microenvironment

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(2)

Published: Sept. 25, 2023

Unsatisfied tumor accumulation of chemotherapeutic drugs and a complicated immunosuppressive microenvironment diminish the immune response rate therapeutic effect. Surface modification these with target ligands can promote their cellular internalization, but modified may be subjected to unexpected recognition clearance. Herein, phenylboronic acid (PBA) group-shieldable dendritic nanomedicine that integrates an immunogenic cell death (ICD)-inducing agent (epirubicin, Epi) indoleamine 2,3-dioxgenase 1 (IDO1) inhibitor (NLG919) is reported for chemo-immunotherapy. This NLG919-loaded Epi-conjugated PEGylated dendrimers bridged boronate bonds (NLG919@Epi-DBP) maintains stable nanostructure during circulation. Under moderate acidic condition, PBA group exposes sialic residue on membrane enhance internalization penetration NLG919@Epi-DBP. At pH 5.0, NLG919@Epi-DBP rapidly disassembles release incorporated Epi NLG919. triggers robust ICD cells evokes strong response. In addition, inhibition IDO1 activity downregulates metabolism L-tryptophan kynurenine, leading reduction in recruitment modulation microenvironment. Collectively, this promising strategy has been demonstrated evoke as well remodel enhanced chemo-immunotherapeutic

Language: Английский

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Platelet-derived drug delivery systems: Pioneering treatment for cancer, cardiovascular diseases, infectious diseases, and beyond

Biomaterials, Journal Year: 2024, Volume and Issue: 306, P. 122478 - 122478

Published: Jan. 21, 2024

Language: Английский

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Inhalable nanovesicles loaded with a STING agonist enhance CAR-T cell activity against solid tumors in the lung

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Suppression of chimeric antigen receptor-modified T (CAR-T) cells by the immunosuppressive tumor microenvironment remains a major barrier to their efficacy against solid tumors. To address this, we develop an anti-PD-L1-expressing nanovesicle loaded with STING agonist cGAMP (aPD-L1 NVs@cGAMP) remodel and thereby enhance CAR-T cell activity. Following pulmonary delivery, nanovesicles rapidly accumulate in lung selectively deliver agonists PD-L1-overexpressing via PD-1/PD-L1 interaction. This targeted delivery effectively avoids systemic inflammation poor cellular uptake that plague free agonists. Internalized trigger signaling induce interferon responses, which diminish populations such as myeloid-derived suppressor promote infiltration. Importantly, anti-PD-L1 single chain variable fragment on surface blocks PD-L1 upregulation induced prevents exhaustion. In both orthotopic cancer metastasis model, combined therapy aPD-L1 NVs@cGAMP potently inhibits growth recurrence. Therefore, is expected serve effective enhancer improve The hindered Here authors report design characterization inhalable cGAMP, showing enhanced activity models.

Language: Английский

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Dendritic Cell-Derived Exosomes in Cancer Immunotherapy

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(8), P. 2070 - 2070

Published: Aug. 1, 2023

Exosomes are nanoscale vesicles released by diverse types of cells for complex intercellular communication. Numerous studies have shown that exosomes can regulate the body’s immune response to tumor and interfere with microenvironment (TME). In clinical trials on dendritic cell (DC)-based antitumor vaccines, no satisfactory results been achieved. However, recent suggested DC-derived (DEXs) may be superior DC-based vaccines in avoiding cell-mediated immunosuppression. DEXs contain multiple surface markers capture tumor-associated antigens (TAAs) promote cell-dependent rejection. These findings indicate necessity further development improvement DEX-based cell-free complement chemotherapy, radiotherapy, other immunotherapies. this review, we highlighted progress cancer immunotherapy, particularly concentrating landmark biological characterization DEXs, summarized their important role (TIME) application targeted immunotherapy. This review could enhance comprehension advances immunotherapy contribute elucidation how TIME, thereby providing a reference utilizing practice.

Language: Английский

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Exosome nanovesicles as potential biomarkers and immune checkpoint signaling modulators in lung cancer microenvironment: recent advances and emerging concepts

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: Aug. 29, 2023

Abstract Lung cancer remains the leading cause of cancer-related deaths globally, and survival rate low despite advances in diagnosis treatment. The progression lung is a multifaceted dynamic phenomenon that encompasses interplays among cancerous cells their microenvironment, which incorporates immune cells. Exosomes, are small membrane-bound vesicles, released by numerous cell types normal stressful situations to allow communication between Tumor-derived exosomes (TEXs) possess diverse neo-antigens cargoes such as proteins, RNA, DNA have unique molecular makeup reflecting tumor genetic complexity. TEXs contain both immunosuppressive immunostimulatory factors may play role immunomodulation influencing innate adaptive components. Moreover, they transmit signals contribute promoting metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, immunosuppression. This makes them valuable resource for investigating environment tumors, could pave way development non-invasive biomarkers aid prognosis, diagnosis, immunotherapy cancer. While checkpoint inhibitor (ICI) has shown promising results treating initial-stage cancers, most patients eventually develop resistance over time. Emerging evidence demonstrates serve prognostic biomarker immunotherapeutic response significant impact on systemic suppression advancement. Therefore, understanding tumorigenesis immunotherapies an exciting research area needs further investigation. review highlights key contributors advancement clinical significance immune-oncology, including possible use monitoring disease well emerging shreds regarding possibility using targets improve therapy.

Language: Английский

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Immune cell-derived extracellular vesicles for precision therapy of inflammatory-related diseases

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 368, P. 533 - 547

Published: March 12, 2024

Language: Английский

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Exosomal miR‐181d‐5p Derived from Rapamycin‐Conditioned MDSC Alleviated Allograft Rejection by Targeting KLF6

Advanced Science, Journal Year: 2023, Volume and Issue: 10(34)

Published: Oct. 23, 2023

Abstract Immune rejection and side effects of long‐term administration immunosuppressants are the two major obstacles to allograft acceptance tolerance. The immunosuppressive extracellular vesicles (EVs)‐based approach has been proven be effective in treating autoimmune/inflammatory disorders. Herein, anti‐rejection advantage exosomes (Rapa‐Exo) from rapamycin‐conditioned myeloid‐derived suppressor cells (MDSCs) over (Exo‐Nor) untreated MDSCs is shown. exosomal small RNA sequencing loss‐of‐function assays reveal that effect Rapa‐Exo functionally relies on miR‐181d‐5p. Through target prediction double‐luciferase reporter assay, Kruppel‐like factor (KLF) 6 identified as a direct Finally, KLF6 knockdown markedly resolves inflammation prolongs survival corneal allografts. Taken together, these findings support executes an effect, highlighting EVs‐based treatment promising organ transplantation.

Language: Английский

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M1-polarized macrophage-derived cellular nanovesicle-coated lipid nanoparticles for enhanced cancer treatment through hybridization of gene therapy and cancer immunotherapy

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(7), P. 3169 - 3183

Published: March 7, 2024

Optimum genetic delivery for modulating target genes to diseased tissue is a major obstacle profitable gene therapy. Lipid nanoparticles (LNPs), considered prospective vehicle nucleic acid delivery, have demonstrated efficacy in human use during the COVID-19 pandemic. This study introduces novel biomaterial-based platform, M1-polarized macrophage-derived cellular nanovesicle-coated LNPs (M1-C-LNPs), specifically engineered combined gene-immunotherapy approach against solid tumor. The dual-function system of M1-C-LNPs encapsulates Bcl2-targeting siRNA within and immune-modulating cytokines M1 nanovesicles (M1-NVs), effectively facilitating apoptosis cancer cells without impacting T NK cells, which activate intratumoral immune response promote granule-mediating killing tumor eradication. Enhanced retention was observed upon administration M1-C-LNPs, owing presence adhesion molecules on M1-NVs, thereby contributing superior growth inhibition. These findings represent promising strategy development targeted effective nanoparticle-based genetic-immunotherapy, with significant implications advancing biomaterial therapeutics.

Language: Английский

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Genetically Engineered Cellular Nanovesicles: Theories, Design and Perspective

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(46)

Published: July 1, 2024

Abstract The use of cellular nanovesicles (CNVs) is a groundbreaking innovation in biomedical applications. Both natural extracellular vesicles (EVs) and artificial cell membrane (AVs) have emerged as innovative CNVs, but they limitations therapeutic effects targeting abilities. Challenges such stability, immunogenicity, drug payload capacity hinder their widespread application. Genetic engineering has matured widely employed modification strategy, leading to the development genetically engineered (gEVs) (gAVs). This review meticulously examines diverse types inherent characteristics alongside various surface strategies for with specific focus on elucidating attributes detailing preparation methods relevant gEVs gAVs. Furthermore, this exploration delves into expansive landscape applications, developmental prospects, current challenges associated utilization With comprehensive approach, primary objective provide insights that not only illuminate nuanced intricacies these also pave way seamless integration clinical research eventual translation practical

Language: Английский

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Biomimetic Nanoparticles for Basic Drug Delivery

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(10), P. 1306 - 1306

Published: Oct. 7, 2024

Biomimetic nanoparticles (BMNPs) are innovative nanovehicles that replicate the properties of naturally occurring extracellular vesicles, facilitating highly efficient drug delivery across biological barriers to target organs and tissues while ensuring maximal biocompatibility minimal-to-no toxicity. BMNPs can be utilized for therapeutic payloads imparting novel other nanotechnologies based on organic inorganic materials. The application specifically modified membranes coating has potential enhance their efficacy biocompatibility, presenting a promising pathway advancement technologies. This manuscript is grounded in fundamentals biomimetic technologies, offering comprehensive overview analytical perspective preparation functionalization BMNPs, which include cell membrane-coated (CMCNPs), artificial cell-derived vesicles (ACDVs), fully synthetic (fSVs). review examines both "top-down" "bottom-up" approaches nanoparticle preparation, with particular focus techniques such as membrane coating, cargo loading, microfluidic fabrication. Additionally, it addresses technological challenges solutions associated large-scale production clinical related

Language: Английский

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