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

International journal of nanomedicine 2022

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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) dimerization blocker, Stattic (S) into a chitosan-coated-poly(lactic-co-glycolic acid) (C-PLGA) nanocarrier and the improvement on the drug's physicochemical, in vitro and in vivo antimetastatic properties post entrapment. 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. 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). These findings suggest the usage of C-PLGA nanocarrier to improve the delivery and efficacy of antimetastatic agents, such as Stattic, in cancer therapy. © 2022 Fong et al.

Citation

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. Chitosan-Coated-PLGA Nanoparticles Enhance the Antitumor and Antimigration Activity of Stattic - A STAT3 Dimerization Blocker. International journal of nanomedicine. 2022;17:137-150