Drug Delivery (Jan 2017)

Self-delivering prodrug-nanoassemblies fabricated by disulfide bond bridged oleate prodrug of docetaxel for breast cancer therapy

  • Shenwu Zhang,
  • Jibin Guan,
  • Mengchi Sun,
  • Dong Zhang,
  • Haotian Zhang,
  • Bingjun Sun,
  • Weiling Guo,
  • Bin Lin,
  • Yongjun Wang,
  • Zhonggui He,
  • Cong Luo,
  • Jin Sun

DOI
https://doi.org/10.1080/10717544.2017.1381201
Journal volume & issue
Vol. 24, no. 1
pp. 1460 – 1469

Abstract

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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.

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