Co-Administration of Tretinoin Enhances the Anti-Cancer Efficacy of Etoposide via Tumor-Targeted Green Nano-Micelles

Mohamed Gaber; Kholod A. Elhasany; Saly Sabra; Maged W. Helmy; Jia You Fang; Sherine N. Khattab; Adnan A. Bekhit; Mohamed Teleb; Kadria A. Elkodairy; Ahmed O. Elzoghby

doi:10.1016/j.colsurfb.2020.110997

Co-Administration of Tretinoin Enhances the Anti-Cancer Efficacy of Etoposide via Tumor-Targeted Green Nano-Micelles

Mohamed Gaber, Kholod A. Elhasany, Saly Sabra, Maged W. Helmy, Jia You Fang, Sherine N. Khattab^*, Adnan A. Bekhit, Mohamed Teleb, Kadria A. Elkodairy, Ahmed O. Elzoghby

^*Corresponding author for this work

School of Traditional Chinese Medicine

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

27 Scopus citations

Abstract

Herein we report promoted anti-cancer activity via a combination strategy of synergistic chemotherapy/retinoid-based breast cancer therapy with shell-stabilized micellar green nanomedicine. Amphiphilic zein-chondroitin sulfate (ChS)-based copolymeric micelles (PMs) were successfully developed via carbodiimide coupling for concomitant delivery of etoposide (ETP) and all-trans retinoic acid (ATRA) to breast cancer. The micelles exhibited low critical micellar concentration (CMC) of 0.008 mg/mL with high encapsulation efficiencies of ETP and ATRA (61.2 and 84.29%, respectively). Calcium-mediated crosslinking of the anionic ChS micellar shell resulted in prolonged drug release with small micellar size of 222.7 nm. The micelles exhibited augmented internalization into MCF-7 breast cancer cells by virtue of ChS binding affinity to CD44 receptors overexpressed by cancer cells. Consequently, the ETP/ATRA-loaded micelles exhibited synergistic cytotoxicity against breast cancer cells as revealed by their significantly lower IC₅₀, combination index (CI), and higherdose reduction index (DRI) in comparison to the free ETP and free ATRA or their combination. Micelles displayed superiority in reducing tumor volume, decreasing proliferation, and promoting necrosis in mice bearing Ehrlich Ascites Tumor (EAT) upon comparison to free ETP and free ATRA or their combination. Overall, the developed green zein-ChS micelles offer a promising platform for tumor-targeted delivery of hydrophobic therapeutic agents.

Original language	English
Article number	110997
Journal	Colloids and Surfaces B: Biointerfaces
Volume	192
DOIs	https://doi.org/10.1016/j.colsurfb.2020.110997
State	Published - 08 2020

Bibliographical note

Publisher Copyright:
© 2020 Elsevier B.V.

Keywords

Amphiphilic co-polymeric micelles
Breast cancer
CD44 receptor targeting
Green nanomedicine
Shell-crosslinked micelles
Synergistic cancer therapy

UN SDGs

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

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10.1016/j.colsurfb.2020.110997

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Gaber, M., Elhasany, K. A., Sabra, S., Helmy, M. W., Fang, J. Y., Khattab, S. N., Bekhit, A. A., Teleb, M., Elkodairy, K. A., & Elzoghby, A. O. (2020). Co-Administration of Tretinoin Enhances the Anti-Cancer Efficacy of Etoposide via Tumor-Targeted Green Nano-Micelles. Colloids and Surfaces B: Biointerfaces, 192, Article 110997. https://doi.org/10.1016/j.colsurfb.2020.110997

@article{828a4659c3cd4a5fbb549ea4e8c7d94c,

title = "Co-Administration of Tretinoin Enhances the Anti-Cancer Efficacy of Etoposide via Tumor-Targeted Green Nano-Micelles",

abstract = "Herein we report promoted anti-cancer activity via a combination strategy of synergistic chemotherapy/retinoid-based breast cancer therapy with shell-stabilized micellar green nanomedicine. Amphiphilic zein-chondroitin sulfate (ChS)-based copolymeric micelles (PMs) were successfully developed via carbodiimide coupling for concomitant delivery of etoposide (ETP) and all-trans retinoic acid (ATRA) to breast cancer. The micelles exhibited low critical micellar concentration (CMC) of 0.008 mg/mL with high encapsulation efficiencies of ETP and ATRA (61.2 and 84.29%, respectively). Calcium-mediated crosslinking of the anionic ChS micellar shell resulted in prolonged drug release with small micellar size of 222.7 nm. The micelles exhibited augmented internalization into MCF-7 breast cancer cells by virtue of ChS binding affinity to CD44 receptors overexpressed by cancer cells. Consequently, the ETP/ATRA-loaded micelles exhibited synergistic cytotoxicity against breast cancer cells as revealed by their significantly lower IC50, combination index (CI), and higherdose reduction index (DRI) in comparison to the free ETP and free ATRA or their combination. Micelles displayed superiority in reducing tumor volume, decreasing proliferation, and promoting necrosis in mice bearing Ehrlich Ascites Tumor (EAT) upon comparison to free ETP and free ATRA or their combination. Overall, the developed green zein-ChS micelles offer a promising platform for tumor-targeted delivery of hydrophobic therapeutic agents.",

keywords = "Amphiphilic co-polymeric micelles, Breast cancer, CD44 receptor targeting, Green nanomedicine, Shell-crosslinked micelles, Synergistic cancer therapy",

author = "Mohamed Gaber and Elhasany, {Kholod A.} and Saly Sabra and Helmy, {Maged W.} and Fang, {Jia You} and Khattab, {Sherine N.} and Bekhit, {Adnan A.} and Mohamed Teleb and Elkodairy, {Kadria A.} and Elzoghby, {Ahmed O.}",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier B.V.",

year = "2020",

month = aug,

doi = "10.1016/j.colsurfb.2020.110997",

language = "英语",

volume = "192",

journal = "Colloids and Surfaces B: Biointerfaces",

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T1 - Co-Administration of Tretinoin Enhances the Anti-Cancer Efficacy of Etoposide via Tumor-Targeted Green Nano-Micelles

AU - Gaber, Mohamed

AU - Elhasany, Kholod A.

AU - Sabra, Saly

AU - Helmy, Maged W.

AU - Fang, Jia You

AU - Khattab, Sherine N.

AU - Bekhit, Adnan A.

AU - Teleb, Mohamed

AU - Elkodairy, Kadria A.

AU - Elzoghby, Ahmed O.

PY - 2020/8

Y1 - 2020/8

N2 - Herein we report promoted anti-cancer activity via a combination strategy of synergistic chemotherapy/retinoid-based breast cancer therapy with shell-stabilized micellar green nanomedicine. Amphiphilic zein-chondroitin sulfate (ChS)-based copolymeric micelles (PMs) were successfully developed via carbodiimide coupling for concomitant delivery of etoposide (ETP) and all-trans retinoic acid (ATRA) to breast cancer. The micelles exhibited low critical micellar concentration (CMC) of 0.008 mg/mL with high encapsulation efficiencies of ETP and ATRA (61.2 and 84.29%, respectively). Calcium-mediated crosslinking of the anionic ChS micellar shell resulted in prolonged drug release with small micellar size of 222.7 nm. The micelles exhibited augmented internalization into MCF-7 breast cancer cells by virtue of ChS binding affinity to CD44 receptors overexpressed by cancer cells. Consequently, the ETP/ATRA-loaded micelles exhibited synergistic cytotoxicity against breast cancer cells as revealed by their significantly lower IC50, combination index (CI), and higherdose reduction index (DRI) in comparison to the free ETP and free ATRA or their combination. Micelles displayed superiority in reducing tumor volume, decreasing proliferation, and promoting necrosis in mice bearing Ehrlich Ascites Tumor (EAT) upon comparison to free ETP and free ATRA or their combination. Overall, the developed green zein-ChS micelles offer a promising platform for tumor-targeted delivery of hydrophobic therapeutic agents.

AB - Herein we report promoted anti-cancer activity via a combination strategy of synergistic chemotherapy/retinoid-based breast cancer therapy with shell-stabilized micellar green nanomedicine. Amphiphilic zein-chondroitin sulfate (ChS)-based copolymeric micelles (PMs) were successfully developed via carbodiimide coupling for concomitant delivery of etoposide (ETP) and all-trans retinoic acid (ATRA) to breast cancer. The micelles exhibited low critical micellar concentration (CMC) of 0.008 mg/mL with high encapsulation efficiencies of ETP and ATRA (61.2 and 84.29%, respectively). Calcium-mediated crosslinking of the anionic ChS micellar shell resulted in prolonged drug release with small micellar size of 222.7 nm. The micelles exhibited augmented internalization into MCF-7 breast cancer cells by virtue of ChS binding affinity to CD44 receptors overexpressed by cancer cells. Consequently, the ETP/ATRA-loaded micelles exhibited synergistic cytotoxicity against breast cancer cells as revealed by their significantly lower IC50, combination index (CI), and higherdose reduction index (DRI) in comparison to the free ETP and free ATRA or their combination. Micelles displayed superiority in reducing tumor volume, decreasing proliferation, and promoting necrosis in mice bearing Ehrlich Ascites Tumor (EAT) upon comparison to free ETP and free ATRA or their combination. Overall, the developed green zein-ChS micelles offer a promising platform for tumor-targeted delivery of hydrophobic therapeutic agents.

KW - Amphiphilic co-polymeric micelles

KW - Breast cancer

KW - CD44 receptor targeting

KW - Green nanomedicine

KW - Shell-crosslinked micelles

KW - Synergistic cancer therapy

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U2 - 10.1016/j.colsurfb.2020.110997

DO - 10.1016/j.colsurfb.2020.110997

M3 - 文章

C2 - 32361378

AN - SCOPUS:85083818335

SN - 0927-7765

VL - 192

JO - Colloids and Surfaces B: Biointerfaces

JF - Colloids and Surfaces B: Biointerfaces

M1 - 110997

ER -

Co-Administration of Tretinoin Enhances the Anti-Cancer Efficacy of Etoposide via Tumor-Targeted Green Nano-Micelles

Abstract

Bibliographical note

Keywords

UN SDGs

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