Chitosan-Coated-PLGA Nanoparticles Enhance the Antitumor and Antimigration Activity of Stattic – A STAT3 Dimerization Blocker

Stephanie Sally Fong, Yiing Yee Foo, Wen Shang Saw, Bey Fen Leo, Yin Yin Teo, Ivy Chung, Boon Tong Goh, Misni Misran, Toyoko Imae, Chia Ching Chang*, Lip Yong Chung, Lik Voon Kiew*

*此作品的通信作者

研究成果: Article同行評審

24 引文 斯高帕斯(Scopus)

摘要

Purpose: The use of nanocarriers to improve the delivery and efficacy of antimetastatic agents is less explored when compared to cytotoxic agents. This study reports the entrapment of an antimetastatic Signal Transducer and Activator of Transcription 3 (STAT3) dimeriza-tion blocker, Stattic (S) into a chitosan-coated-poly(lactic-co-glycolic acid) (C-PLGA) nano-carrier and the improvement on the drug’s physicochemical, in vitro and in vivo antimetastatic properties post entrapment. Methods: In vitro, physicochemical properties of the Stattic-entrapped C-PLGA nanoparticles (S@C-PLGA) and Stattic-entrapped PLGA nanoparticles (S@PLGA, control) in terms of size, zeta potential, polydispersity index, drug loading, entrapment efficiency, Stattic release in different medium and cytotoxicity were firstly evaluated. The in vitro antimigration properties of the nanoparticles on breast cancer cell lines were then studied by Scratch assay and Transwell assay. Study on the in vivo antitumor efficacy and antimetastatic properties of S@C-PLGA compared to Stattic were then performed on 4T1 tumor bearing mice. Results: The S@C-PLGA nanoparticles (141.8 ± 2.3 nm) was hemocompatible and exhibited low Stattic release (12%) in plasma. S@C-PLGA also exhibited enhanced in vitro anti-cell migration potency (by >10-fold in MDA-MB-231 and 5-fold in 4T1 cells) and in vivo tumor growth suppression (by 33.6%) in 4T1 murine metastatic mammary tumor bearing mice when compared to that of the Stattic-treated group. Interestingly, the number of lung and liver metastatic foci was found to reduce by 50% and 56.6%, respectively, and the average size of the lung metastatic foci was reduced by 75.4% in 4T1 tumor-bearing mice treated with S@C-PLGA compared to Stattic-treated group (p < 0.001). Conclusion: These findings suggest the usage of C-PLGA nanocarrier to improve the delivery and efficacy of antimetastatic agents, such as Stattic, in cancer therapy.

原文English
頁(從 - 到)137-150
頁數14
期刊International Journal of Nanomedicine
17
DOIs
出版狀態Published - 2022

指紋

深入研究「Chitosan-Coated-PLGA Nanoparticles Enhance the Antitumor and Antimigration Activity of Stattic – A STAT3 Dimerization Blocker」主題。共同形成了獨特的指紋。

引用此