Engineering TGF-β inhibitor-encapsulated macrophage-inspired multi-functional nanoparticles for combination cancer immunotherapy

Background The emergence of cancer immunotherapies, notably immune checkpoint inhibitors, has revolutionized anti-cancer treatments. These treatments, however, have been reported to be effective in a limited range of cancers and cause immune-related adverse effects. Thus, for a broader applicability...

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Veröffentlicht in:Biomaterials research Jg. 27; H. 1; S. 136 - 3084
Hauptverfasser: Kim, Jaehyun, Kim, Minjeong, Yong, Seok-Beom, Han, Heesoo, Kang, Seyoung, Lahiji, Shayan Fakhraei, Kim, Sangjin, Hong, Juhyeong, Seo, Yuha, Kim, Yong-Hee
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London BioMed Central 18.12.2023
한국생체재료학회
Schlagworte:
Biomaterials
Bone marrow
Breast cancer
Cancer immunotherapy
Cancer therapies
Cancer vaccines
Cells
Chemistry and Materials Science
Clinical trials
Cytokines
Cytotoxicity
Immune checkpoint inhibitors
Immunomodulation
Immunostimulation
Immunotherapy
Kinases
Lymphocytes T
Macrophages
Materials Science
Membranes
Metastases
Metastasis
Monoclonal antibodies
Nanoparticles
Nanotechnology
PD-1 protein
Penicillin
Proteins
Research Article
Response rates
Solid tumors
Transforming growth factor-b
Tumor microenvironment
의공학
United States > US
Immune cell-inspired nanoparticle
TGF-β inhibition
Tumor-associated macrophage
Immune checkpoint inhibitor
Cancer immunotherapy
Combination therapy
ISSN:2055-7124, 1226-4601, 2055-7124
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Zusammenfassung:Background The emergence of cancer immunotherapies, notably immune checkpoint inhibitors, has revolutionized anti-cancer treatments. These treatments, however, have been reported to be effective in a limited range of cancers and cause immune-related adverse effects. Thus, for a broader applicability and enhanced responsiveness to solid tumor immunotherapy, immunomodulation of the tumor microenvironment is crucial. Transforming growth factor-β (TGF-β) has been implicated in reducing immunotherapy responsiveness by promoting M2-type differentiation of macrophages and facilitating cancer cell metastasis. Methods In this study, we developed macrophage membrane-coated nanoparticles loaded with a TGF-βR1 kinase inhibitor, SD-208 (M -SDNP). Inhibitions of M2 macrophage polarization and epithelial-to-mesenchymal transition (EMT) of cancer cells were comprehensively evaluated through in vitro and in vivo experiments. Bio-distribution study and in vivo therapeutic effects of M -SDNP were investigated in orthotopic breast cancer model and intraveneously injected metastasis model. Results M -SDNPs effectively inhibited cancer metastasis and converted the immunosuppressive tumor microenvironment (cold tumor) into an immunostimulatory tumor microenvironment (hot tumor), through specific tumor targeting and blockade of M2-type macrophage differentiation. Administration of M -SDNPs considerably augmented the population of cytotoxic T lymphocytes (CTLs) in the tumor tissue, thereby significantly enhancing responsiveness to immune checkpoint inhibitors, which demonstrates a robust anti-cancer effect in conjunction with anti-PD-1 antibodies. Conclusion Collectively, responsiveness to immune checkpoint inhibitors was considerably enhanced and a robust anti-cancer effect was demonstrated with the combination treatment of M -SDNPs and anti-PD-1 antibody. This suggests a promising direction for future therapeutic strategies, utilizing bio-inspired nanotechnology to improve the efficacy of cancer immunotherapy. Graphical Abstract
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https://biomaterialsres.biomedcentral.com/counter/pdf/10.1186/s40824-023-00470-y.pdf
ISSN:2055-7124
1226-4601
2055-7124
DOI:10.1186/s40824-023-00470-y