Targeted delivery of pexidartinib to tumor-associated macrophages via legumain-sensitive dual-coating nanoparticles for cancer immunotherapy.
Colloids Surf B Biointerfaces
; 226: 113283, 2023 Jun.
Article
in En
| MEDLINE
| ID: mdl-37030033
ABSTRACT
Tumor-associated macrophage (TAM) is regarded as an appealing cell target for cancer immunotherapy. However, it remains challenging to selectively eliminate M2-like TAM in tumor microenvironment. In this work, we employed a legumain-sensitive dual-coating nanosystem (s-Tpep-NPs) to deliver CSF-1R inhibitor pexidartinib (PLX3397) for targeting TAM therapy. The PLX3397-loaded NPs exhibited uniform size of â¼240 nm in diameter, good drug loading capacity and efficiency, as well as sustained drug release profile. Compared to non-sensitive counterpart ns-Tpep-NPs, s-Tpep-NPs showed distinguished selectivity upon M1 and M2 macrophage uptake with relation to incubation time and dose. Besides, the selectivity of anti-proliferation effect was also identified for s-Tpep-NPs against M1 and M2 macrophage. In vivo imaging demonstrated that s-Tpep-NPs exhibited much higher tumoral accumulation and TAM recognition specificity as compared to non-sensitive ns-Tpep-NPs. In vivo efficacy verified that s-Tpep-NPs formulation was much more effective than ns-Tpep-NPs and other PLX3397 formulations to treat B16F10 melanoma via targeting TAM depletion and modulating tumor immune microenvironment. Overall, this study provides a robust and promising nanomedicine strategy for TAM-targeted cancer immunotherapy.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Nanoparticles
/
Neoplasms
Type of study:
Diagnostic_studies
/
Risk_factors_studies
Language:
En
Journal:
Colloids Surf B Biointerfaces
Journal subject:
QUIMICA
Year:
2023
Type:
Article