Abstract
Breast cancer leads to high mortality of women in the world. Docetaxel (DTX) has been widely applied as one of the first-line chemotherapeutic drugs for breast cancer therapy. However, the clinical outcome of DTX is far from satisfaction due to its poor drug delivery efficiency. Herein, a novel disulfide bond bridged oleate prodrug of DTX was designed and synthesized to construct self-delivering prodrug-based nanosystem for improved anticancer efficacy of DTX. The uniquely engineered prodrug-nanoassemblies showed redox-responsive drug release, increased cellular uptake and comparable cytotoxicity against 4T1 breast cancer cells when compared with free DTX. In vivo, oleate prodrug-based nanoparticles (NPs) demonstrated significantly prolonged systemic circulation and increased accumulation in tumor site. As a result, prodrug NPs produced a notable antitumor activity in 4T1 breast cancer xenograft in BALB/c mice. This prodrug-based self-assembly and self-delivery strategy could be utilized to improve the delivery efficiency of DTX for breast cancer treatment.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1460-1469 |
| Number of pages | 10 |
| Journal | Drug Delivery |
| Volume | 24 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2017 |
| Externally published | Yes |
Bibliographical note
Funding Information:This work was financially supported by the National Basic Research Program of China [973 Program, No. 2015CB932100], the National Nature Science Foundation of China [No. 81273450, 81373336, 81473164 and 81703451], and China Postdoctoral Science Foundation Grant [No. 2017M611269].
Publisher Copyright:
© 2017 The Author(s).
Keywords
- Breast cancer
- Docetaxel
- Oleate prodrug
- Self-assembly
- Self-delivery
