ZIF-8-Encapsulated Pexidartinib Delivery via Targeted Peptide-Modified M1 Macrophages Attenuates MDSC-Mediated Immunosuppression in Osteosarcoma.
Small
; 20(29): e2309038, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38456768
ABSTRACT
Adoptive cellular therapy is a promising strategy for cancer treatment. However, the effectiveness of this therapy is limited by its intricate and immunosuppressive tumor microenvironment. In this study, a targeted therapeutic strategy for macrophage loading of drugs is presented to enhance anti-tumor efficacy of macrophages. K7M2-target peptide (KTP) is used to modify macrophages to enhance their affinity for tumors. Pexidartinib-loaded ZIF-8 nanoparticles (P@ZIF-8) are loaded into macrophages to synergistically alleviate the immunosuppressive tumor microenvironment synergistically. Thus, the M1 macrophages decorated with KTP carried P@ZIF-8 and are named P@ZIF/M1-KTP. The tumor volumes in the P@ZIF/M1-KTP group are significantly smaller than those in the other groups, indicating that P@ZIF/M1-KTP exhibited enhanced anti-tumor efficacy. Mechanistically, an increased ratio of CD4+ T cells and a decreased ratio of MDSCs in the tumor tissues after treatment with P@ZIF/M1-KTP indicated that it can alleviate the immunosuppressive tumor microenvironment. RNA-seq further confirms the enhanced immune cell function. Consequently, P@ZIF/M1-KTP has great potential as a novel adoptive cellular therapeutic strategy for tumors.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Osteossarcoma
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Zeolitas
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Microambiente Tumoral
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Células Supressoras Mieloides
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Macrófagos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Small
/
Small (Weinh., Internet)
/
Small (Weinheim. Internet)
Assunto da revista:
ENGENHARIA BIOMEDICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China