Chitosan-coated-PLGA nanoparticles enhance the antitumor and antimigration activity of stattic : A STAT3 dimerization blocker

• Main Authors: Fong, Stephanie Sally, Foo, Yiing Yee, Saw, Wen Shang, Leo, Bey Fen, Teo, Yin Yin, Chung, Ivy, Goh, Boon Tong, Misran, Misni, Imae, Toyoko, Chang, Chia-Ching, Chung, Lip Yong, Kiew, Lik Voon
• Format: Article
• Published: Dove Medical Press 2022
• Subjects: Q Science (General); R Medicine; RC0254 Neoplasms. Tumors. Oncology (including Cancer); RD Surgery
• Online Access: http://eprints.um.edu.my/33542/

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 exhib-ited 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.