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

Fong, Stephanie Sally and Foo, Yiing Yee and Saw, Wen Shang and Leo, Bey Fen and Teo, Yin Yin and Chung, Ivy and Goh, Boon Tong and Misran, Misni and Imae, Toyoko and Chang, Chia-Ching and Chung, Lip Yong and Kiew, Lik Voon (2022) Chitosan-coated-PLGA nanoparticles enhance the antitumor and antimigration activity of stattic : A STAT3 dimerization blocker. International Journal of Nanomedicine, 17. pp. 137-150. ISSN 1176-9114, DOI

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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.

Item Type: Article
Funders: Ministry of Education, Malaysia[FRGS/1/2017/SKK10/UM/02/1], MOST grants of Taiwan[MOST 107-2112-M-009-016-MY3], MOST grants of Taiwan[MOST 109-2811-M-009-502]
Uncontrolled Keywords: Nanocarrier;STAT3 protein;Breast cancer;Metastasis;Chitosan-coating
Subjects: Q Science > Q Science (General)
R Medicine
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RD Surgery
Divisions: Faculty of Medicine
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 04 Aug 2022 03:39
Last Modified: 04 Aug 2022 03:39

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