Tumor microenvironment responsive nano-herb and CRISPR delivery system for synergistic chemotherapy and immunotherapy.
J Nanobiotechnology
; 22(1): 346, 2024 Jun 19.
Article
in En
| MEDLINE
| ID: mdl-38898493
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Doxorubicin
/
Tumor Microenvironment
/
Immunotherapy
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
J Nanobiotechnology
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
United kingdom