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Sulforaphane mediates glutathione depletion via polymeric nanoparticles to restore cisplatin chemosensitivity
- Publication Year :
- 2019
-
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.
- Subjects :
- Cell Survival
Polymers
medicine.medical_treatment
General Physics and Astronomy
Mice, Nude
Antineoplastic Agents
Apoptosis
Breast Neoplasms
02 engineering and technology
010402 general chemistry
01 natural sciences
chemistry.chemical_compound
Mice
Liver Neoplasms, Experimental
Isothiocyanates
medicine
Tumor Cells, Cultured
Distribution (pharmacology)
Animals
Humans
General Materials Science
Cell Proliferation
Cisplatin
Chemotherapy
Mice, Inbred BALB C
Chemistry
Optical Imaging
General Engineering
Mammary Neoplasms, Experimental
Glutathione
Hep G2 Cells
021001 nanoscience & nanotechnology
medicine.disease
0104 chemical sciences
Sulfoxides
Cancer cell
Cancer research
MCF-7 Cells
Nanoparticles
Female
Drug Screening Assays, Antitumor
0210 nano-technology
Liver cancer
medicine.drug
Sulforaphane
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....7b49a67882bbb78ac8406d267afd681a