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 ORCID: https://orcid.org/0000-0003-1872-9572, Bao, Yongping ORCID: https://orcid.org/0000-0002-6425-0370 and Nie, Guangjun (2019) Sulforaphane mediates glutathione depletion via polymeric nanoparticles to restore cisplatin chemosensitivity. ACS Nano, 13 (11). pp. 13445-13455. ISSN 1936-0851

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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.

Item Type:	Article
Uncontrolled Keywords:	sulforaphane,cisplatin,glutathione,nanoparticle,breast cancer,sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School Faculty of Science > School of Pharmacy (former - to 2024)
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies Faculty of Science > Research Groups > Pharmaceutical Materials and Soft Matter Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Depositing User:	LivePure Connector
Date Deposited:	04 Nov 2019 09:30
Last Modified:	15 Dec 2024 01:21
URI:	https://ueaeprints.uea.ac.uk/id/eprint/72854
DOI:	10.1021/acsnano.9b07032

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