Sulforaphane Mediates Glutathione Depletion via Polymeric Nanoparticles to Restore Cisplatin Chemosensitivity
Xu Y, Han X, Li Y, Min H, Zhao X, Zhang Y, Qi Y, Shi J, Qi S, Bao Y, Nie G
ACS nano · 111 citations
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Clinical events such as disease or death
Who paid for it
- Funding
- Independent funding
- Nonprofit
- Cancer Prevention Research Trust
- Nonprofit
- Academy of Medical Sciences
- Government
- National Natural Science Foundation of China
- University or hospital
- Chinese Academy of Sciences
- Government
- Ministry of Science and Technology of the People's Republic of China
- Nonprofit
- K. C. Wong Education Foundation
- University or hospital
- Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety
- Government
- Ministry of Science and Technology of the People's Republic of China
- Grants
- National Natural Science Foundation of China (2016YFA0201600); National Natural Science Foundation of China (31571021); K. C. Wong Education Foundation (GJTD2018-03); Chinese Academy of Sciences (2018YFA0208900); Chinese Academy of Sciences (2016YFA0201600); National Natural Science Foundation of China (11621505); Chinese Academy of Sciences (11621505); National Natural Science Foundation of China (QYZDJ‐SSW‐SLH022); Academy of Medical Sciences (NAF003\1002); Chinese Academy of Sciences (QYZDJ-SSW-SLH022); Ministry of Science and Technology of the People's Republic of China (2016YFA0201600); National Natural Science Foundation of China (2018YFA0208900); Ministry of Science and Technology of the People's Republic of China (2018YFA0208900)
Based on 8 listed funder(s).
Publication
- Published
- 2019-10-31 · ACS Nano · vol. 13 · issue 11 · pp. 13445–13455
- Publisher
- American Chemical Society
- Cited
- 147 citations · more than 99% of similar papers · 9.8× the field average
- Impact
- Top 10% most cited in its field
- References
- 45 works
- Access
- Open access (repository copy)
- Research areas
- Chemotherapy-induced organ toxicity mitigation · Genomics, phytochemicals, and oxidative stress · Sulfur Compounds in Biology
- Keywords
- Sulforaphane, Cisplatin, Glutathione, Nanoparticle, Chemistry, Biophysics, Nanotechnology, Combinatorial chemistry, Biochemistry, Materials science, Enzyme, Chemotherapy, Medicine, Biology
- MeSH
- tumor cells, cultured, animals, mice, inbred balb c, humans, mice, mice, nude, breast neoplasms, liver neoplasms, experimental, mammary neoplasms, experimental, cisplatin, isothiocyanates, sulfoxides, polymers, glutathione, antineoplastic agents, drug screening assays, antitumor, apoptosis, cell proliferation, cell survival, female, nanoparticles, hep g2 cells, mcf-7 cells, optical imaging
11 authors
From CN, GB
- Ying XuSino-Danish Centre for Education and Research; National Center for Nanoscience and Technology; University of Chinese Academy of Sciences
- Xuexiang HanNational Center for Nanoscience and Technology; University of Chinese Academy of Sciences; Tsinghua University
- Yiye Li · correspondingNational Center for Nanoscience and Technology; University of Chinese Academy of Sciences
- Huan MinNational Center for Nanoscience and Technology
- Xiao ZhaoNational Center for Nanoscience and Technology; University of Chinese Academy of Sciences
- Yinlong ZhangNational Center for Nanoscience and Technology; University of Chinese Academy of Sciences
Abstract
Platinum (Pt)-based chemotherapy is a broadly 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 codeliver 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 improve 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 antitumor activity. Finally, this nanoenhanced chemotherapy was further confirmed in a liver cancer model with high-expression of GSH. Taken together, this sulforaphane-based nanostrategy holds great promise to enhance the sensitivity and therapeutic efficacy of Pt-based chemotherapy.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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