Development of cancer-associated fibroblasts-targeting polymeric nanoparticles loaded with 8-O-methylfusarubin for breast cancer treatment
1
Issued Date
2024-12-01
Resource Type
eISSN
25901567
Scopus ID
2-s2.0-85207030963
Journal Title
International Journal of Pharmaceutics: X
Volume
8
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Journal of Pharmaceutics: X Vol.8 (2024)
Suggested Citation
Rodponthukwaji K., Thongchot S., Deureh S., Thongkleang T., Thaweesuvannasak M., Srichan K., Srisawat C., Thuwajit P., Nguyen K.T., Tadpetch K., Thuwajit C., Punnakitikashem P. Development of cancer-associated fibroblasts-targeting polymeric nanoparticles loaded with 8-O-methylfusarubin for breast cancer treatment. International Journal of Pharmaceutics: X Vol.8 (2024). doi:10.1016/j.ijpx.2024.100294 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/101806
Title
Development of cancer-associated fibroblasts-targeting polymeric nanoparticles loaded with 8-O-methylfusarubin for breast cancer treatment
Corresponding Author(s)
Other Contributor(s)
Abstract
Cancer-associated fibroblasts (CAFs) are abundant stromal cells residing in a tumor microenvironment (TME) which are associated with the progression of tumor. Herein, we developed novel CAFs-targeting polymeric nanoparticles encapsulating a synthetic 8-O-methylfusarubin (OMF) compound (OMF@NPs-anti-FAP). Anti-FAP/fibroblast activation protein antibody was employed as a CAFs-targeting ligand. The physicochemical properties of the synthesized nanomaterials were firstly investigated with various techniques. The cytocompatibility of polymeric nanoparticles (NPs) was elicited through cell viability of CAFs and human breast epithelial cells, MCF-10A. Additionally, the anti-FAP-conjugated NPs displayed different degrees of cellular internalization regarding the FAP expression level on the CAFs' surface. However, CAFs exposed to NPs containing OMF demonstrated significant cell death which were associated with the apoptotic pathway as confirmed by caspase-3/7 activity. Upon OMF@NPs-anti-FAP treatment, an enhanced toxicity was clearly observed in 3D spheroid models. High FAP-expressed PC-B-132CAFs demonstrated a high percentage of cell death compared to other cells with a low level of FAP expression analyzed by flow cytometry (e.g. MCF-10A, HDFa, and PC-B-142CAFs). This result emphasized the importance of anti-FAP antibody as a targeting ligand. These findings suggest that the fabricated nanosystem of OMF-loaded polymeric NPs with CAFs' high specificity holds a potential NP-based platform for improvement in breast cancer treatment.