Tumor microenvironment responsive nano-herb and CRISPR delivery system for synergistic chemotherapy and immunotherapy

Autor: Yuanyuan Jia, Yuhui Yao, Lingyao Fan, Qiqing Huang, Guohao Wei, Peiliang Shen, Jia Sun, Gaoshuang Zhu, Zhaorui Sun, Chuandong Zhu, Xin Han
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Journal of Nanobiotechnology, Vol 22, Iss 1, Pp 1-16 (2024)
Druh dokumentu: article
ISSN: 1477-3155
DOI: 10.1186/s12951-024-02571-9
Popis: Abstract Chemoresistance remains a significant challenge for effective breast cancer treatment which leads to cancer recurrence. CRISPR-directed gene editing becomes a powerful tool to reduce chemoresistance by reprogramming the tumor microenvironment. Previous research has revealed that Chinese herbal extracts have significant potential to overcome tumor chemoresistance. However, the therapeutic efficacy is often limited due to their poor tumor targeting and in vivo durability. Here we have developed a tumor microenvironment responsive nanoplatform (H-MnO2(ISL + DOX)-PTPN2@HA, M(I + D)PH) for nano-herb and CRISPR codelivery to reduce chemoresistance. Synergistic tumor inhibitory effects were achieved by the treatment of isoliquiritigenin (ISL) with doxorubicin (DOX), which were enhanced by CRISPR-based gene editing to target protein tyrosine phosphatase non-receptor type 2 (PTPN2) to initiate long-term immunotherapy. Efficient PTPN2 depletion was observed after treatment with M(I + D)PH nanoparticles, which resulted in the recruitment of intratumoral infiltrating lymphocytes and an increase of proinflammatory cytokines in the tumor tissue. Overall, our nanoparticle platform provides a diverse technique for accomplishing synergistic chemotherapy and immunotherapy, which offers an effective treatment alternative for malignant neoplasms. Graphical Abstract
Databáze: Directory of Open Access Journals
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