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

doi:10.2147/IJN.S337093

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	137-150
Number of pages	14
Journal	International Journal of Nanomedicine
Volume	17
DOIs	https://doi.org/10.2147/IJN.S337093
State	Published - 2022

Keywords

Breast cancer
Chitosan-coating
Metastasis
Nanocarrier
STAT3 protein

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.2147/IJN.S337093

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Fong, S. S., Foo, Y. Y., Saw, W. S., Leo, B. F., Teo, Y. Y., Chung, I., Goh, B. T., Misran, M., Imae, T., Chang, C. C., Chung, L. Y., & Kiew, L. V. (2022). Chitosan-Coated-PLGA Nanoparticles Enhance the Antitumor and Antimigration Activity of Stattic – A STAT3 Dimerization Blocker. International Journal of Nanomedicine, 17, 137-150. https://doi.org/10.2147/IJN.S337093

@article{597ec83b30f44e498d5577542c515232,

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

abstract = "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{\textquoteright}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.",

keywords = "Breast cancer, Chitosan-coating, Metastasis, Nanocarrier, STAT3 protein",

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

note = "Publisher Copyright: {\textcopyright} 2022 Fong et al.",

year = "2022",

doi = "10.2147/IJN.S337093",

language = "English",

volume = "17",

pages = "137--150",

journal = "International Journal of Nanomedicine",

issn = "1176-9114",

publisher = "Dove Medical Press Ltd.",

}

TY - JOUR

T1 - Chitosan-Coated-PLGA Nanoparticles Enhance the Antitumor and Antimigration Activity of Stattic – A STAT3 Dimerization Blocker

AU - Fong, Stephanie Sally

AU - Foo, Yiing Yee

AU - Saw, Wen Shang

AU - Leo, Bey Fen

AU - Teo, Yin Yin

AU - Chung, Ivy

AU - Goh, Boon Tong

AU - Misran, Misni

AU - Imae, Toyoko

AU - Chang, Chia Ching

AU - Chung, Lip Yong

AU - Kiew, Lik Voon

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - Breast cancer

KW - Chitosan-coating

KW - Metastasis

KW - Nanocarrier

KW - STAT3 protein

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U2 - 10.2147/IJN.S337093

DO - 10.2147/IJN.S337093

M3 - Article

C2 - 35046650

AN - SCOPUS:85123813724

SN - 1176-9114

VL - 17

SP - 137

EP - 150

JO - International Journal of Nanomedicine

JF - International Journal of Nanomedicine

ER -

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

Abstract

Keywords

UN SDGs

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