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Sulforaphane Mediates Glutathione Depletion via Polymeric Nanoparticles to Restore Cisplatin Chemosensitivity

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Sulforaphane Mediates Glutathione Depletion via Polymeric Nanoparticles to Restore Cisplatin Chemosensitivity. / Xu, Ying; Han, Xuexiang; Li, Yiye; Min, Huan; Zhao, Xiao; Zhang, Yinlong; Qi, Yingqiu; Shi, Jian; Qi, Sheng; Bao, Yongping; Nie, Guangjun.

In: ACS Nano, Vol. 13, No. 11, 26.11.2019, p. 13445-13455.

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Xu, Y, Han, X, Li, Y, Min, H, Zhao, X, Zhang, Y, Qi, Y, Shi, J, Qi, S, Bao, Y & Nie, G 2019, 'Sulforaphane Mediates Glutathione Depletion via Polymeric Nanoparticles to Restore Cisplatin Chemosensitivity', ACS Nano, vol. 13, no. 11, pp. 13445-13455. https://doi.org/10.1021/acsnano.9b07032

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Xu, Ying ; Han, Xuexiang ; Li, Yiye ; Min, Huan ; Zhao, Xiao ; Zhang, Yinlong ; Qi, Yingqiu ; Shi, Jian ; Qi, Sheng ; Bao, Yongping ; Nie, Guangjun. / Sulforaphane Mediates Glutathione Depletion via Polymeric Nanoparticles to Restore Cisplatin Chemosensitivity. In: ACS Nano. 2019 ; Vol. 13, No. 11. pp. 13445-13455.

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@article{0f544a3651364aa2b2eb29ff8493dc65,
title = "Sulforaphane Mediates Glutathione Depletion via Polymeric Nanoparticles to Restore Cisplatin Chemosensitivity",
abstract = "Platinum (Pt)-based chemotherapy is a widely used therapeutic regimen against various cancers. However, the insufficient cellular uptake, deactivation by thiol-containing species and nonspecific distribution of cisplatin (CDDP) result in its low chemosensitivity as well as systemic side effects, which can largely constrain the employment of CDDP in clinical treatment. To circumvent these problems, in this study, polymeric nanoparticles were utilized to co-deliver a water-soluble CDDP derivative, poly (γ, L-glutamic acid)-CDDP conjugate, and a naturally occurring compound derived from broccoli, sulforaphane, which can achieve efficient glutathione (GSH) depletion, to enhance the accumulation of CDDP in cancer cells. Results show that compared with combinational treatment of CDDP and SFN, the nanoparticles were more effectively internalized and could significantly reduce GSH content in breast cancer cells, leading to a notable increase in DNA-bound Pt and DNA damage-induced apoptosis. Moreover, in an orthotopic breast cancer model, the nanoparticles achieved a significantly higher tumor accumulation and exhibited a more powerful anti-tumor activity. Finally, this nano-enhanced chemotherapy was further confirmed in a liver cancer model with high-expression of GSH. Taken together, this sulforaphane-based nano-strategy holds great promise to enhance the sensitivity and therapeutic efficacy of Pt-based chemotherapy.",
keywords = "Sulforaphane, Cisplatin, Glutathione, Nanoparticle, Breast cancer",
author = "Ying Xu and Xuexiang Han and Yiye Li and Huan Min and Xiao Zhao and Yinlong Zhang and Yingqiu Qi and Jian Shi and Sheng Qi and Yongping Bao and Guangjun Nie",
year = "2019",
month = nov,
day = "26",
doi = "10.1021/acsnano.9b07032",
language = "English",
volume = "13",
pages = "13445--13455",
journal = "ACS Nano",
issn = "1936-0851",
publisher = "American Chemical Society",
number = "11",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Sulforaphane Mediates Glutathione Depletion via Polymeric Nanoparticles to Restore Cisplatin Chemosensitivity

AU - Xu, Ying

AU - Han, Xuexiang

AU - Li, Yiye

AU - Min, Huan

AU - Zhao, Xiao

AU - Zhang, Yinlong

AU - Qi, Yingqiu

AU - Shi, Jian

AU - Qi, Sheng

AU - Bao, Yongping

AU - Nie, Guangjun

PY - 2019/11/26

Y1 - 2019/11/26

N2 - Platinum (Pt)-based chemotherapy is a widely used therapeutic regimen against various cancers. However, the insufficient cellular uptake, deactivation by thiol-containing species and nonspecific distribution of cisplatin (CDDP) result in its low chemosensitivity as well as systemic side effects, which can largely constrain the employment of CDDP in clinical treatment. To circumvent these problems, in this study, polymeric nanoparticles were utilized to co-deliver a water-soluble CDDP derivative, poly (γ, L-glutamic acid)-CDDP conjugate, and a naturally occurring compound derived from broccoli, sulforaphane, which can achieve efficient glutathione (GSH) depletion, to enhance the accumulation of CDDP in cancer cells. Results show that compared with combinational treatment of CDDP and SFN, the nanoparticles were more effectively internalized and could significantly reduce GSH content in breast cancer cells, leading to a notable increase in DNA-bound Pt and DNA damage-induced apoptosis. Moreover, in an orthotopic breast cancer model, the nanoparticles achieved a significantly higher tumor accumulation and exhibited a more powerful anti-tumor activity. Finally, this nano-enhanced chemotherapy was further confirmed in a liver cancer model with high-expression of GSH. Taken together, this sulforaphane-based nano-strategy holds great promise to enhance the sensitivity and therapeutic efficacy of Pt-based chemotherapy.

AB - Platinum (Pt)-based chemotherapy is a widely used therapeutic regimen against various cancers. However, the insufficient cellular uptake, deactivation by thiol-containing species and nonspecific distribution of cisplatin (CDDP) result in its low chemosensitivity as well as systemic side effects, which can largely constrain the employment of CDDP in clinical treatment. To circumvent these problems, in this study, polymeric nanoparticles were utilized to co-deliver a water-soluble CDDP derivative, poly (γ, L-glutamic acid)-CDDP conjugate, and a naturally occurring compound derived from broccoli, sulforaphane, which can achieve efficient glutathione (GSH) depletion, to enhance the accumulation of CDDP in cancer cells. Results show that compared with combinational treatment of CDDP and SFN, the nanoparticles were more effectively internalized and could significantly reduce GSH content in breast cancer cells, leading to a notable increase in DNA-bound Pt and DNA damage-induced apoptosis. Moreover, in an orthotopic breast cancer model, the nanoparticles achieved a significantly higher tumor accumulation and exhibited a more powerful anti-tumor activity. Finally, this nano-enhanced chemotherapy was further confirmed in a liver cancer model with high-expression of GSH. Taken together, this sulforaphane-based nano-strategy holds great promise to enhance the sensitivity and therapeutic efficacy of Pt-based chemotherapy.

KW - Sulforaphane

KW - Cisplatin

KW - Glutathione

KW - Nanoparticle

KW - Breast cancer

U2 - 10.1021/acsnano.9b07032

DO - 10.1021/acsnano.9b07032

M3 - Article

VL - 13

SP - 13445

EP - 13455

JO - ACS Nano

JF - ACS Nano

SN - 1936-0851

IS - 11

ER -

ID: 169017945