Enhanced bioreduction-responsive diselenide-based dimeric prodrug nanoparticles for triple negative breast cancer therapy

Xi He, Jinxiao Zhang, Chao Li, Yu Zhang, Yifei Lu, Yujie Zhang, Lisha Liu, Chunhui Ruan, Qinjun Chen, Xinli Chen, Qin Guo, Tao Sun, Jianjun Cheng, Chen Jiang

Research output: Contribution to journalArticle

Abstract

Efficient drug accumulation in tumor is essential for chemotherapy. We developed redox-responsive diselenide-based high-loading prodrug nanoparticles (NPs) for targeted triple negative breast cancer (TNBC) treatment. Method: Redox-responsive diselenide bond (Se-Se) containing dimeric prodrug (PTXD-Se) was synthesized and co-precipitated with TNBC-targeting amphiphilic copolymers to form ultra-stable NPs (uPA-PTXD NPs). The drug loading capacity and redox-responsive drug release behavior were studied. TNBC targeting effect and anti-tumor effect were also evaluated in vitro and in vivo. Results: On-demand designed paclitaxel dimeric prodrug could co-precipitate with amphiphilic copolymers to form ultra-stable uPA-PTXD NPs with high drug loading capacity. Diselenide bond (Se-Se) in uPA-PTXD NPs could be selectively cleaved by abnormally high reduced potential in tumor microenvironment, releasing prototype drug, thus contributing to improved anti-cancer efficacy. Endowed with TNBC-targeting ligand uPA peptide, uPA-PTXD NPs exhibited reduced systemic toxicity and enhanced drug accumulation in TNBC lesions, thus showed significant anti-tumor efficacy both in vitro and in vivo. Conclusion: The comprehensive advantage of high drug loading, redox-controlled drug release and targeted tumor accumulation suggests uPA-PTXD NPs as a highly promising strategy for effective TNBC treatment.

Original languageEnglish (US)
Pages (from-to)4884-4897
Number of pages14
JournalTheranostics
Volume8
Issue number18
DOIs
StatePublished - Jan 1 2018

Fingerprint

Triple Negative Breast Neoplasms
Prodrugs
Nanoparticles
Oxidation-Reduction
Pharmaceutical Preparations
Neoplasms
Therapeutics
Tumor Microenvironment
Paclitaxel
Drug-Related Side Effects and Adverse Reactions
Ligands
Drug Therapy
Peptides

Keywords

  • Diselenide bond
  • Nanoparticles
  • Prodrugs
  • Redox responsive
  • Triple negative breast cancer

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

Cite this

Enhanced bioreduction-responsive diselenide-based dimeric prodrug nanoparticles for triple negative breast cancer therapy. / He, Xi; Zhang, Jinxiao; Li, Chao; Zhang, Yu; Lu, Yifei; Zhang, Yujie; Liu, Lisha; Ruan, Chunhui; Chen, Qinjun; Chen, Xinli; Guo, Qin; Sun, Tao; Cheng, Jianjun; Jiang, Chen.

In: Theranostics, Vol. 8, No. 18, 01.01.2018, p. 4884-4897.

Research output: Contribution to journalArticle

He, X, Zhang, J, Li, C, Zhang, Y, Lu, Y, Zhang, Y, Liu, L, Ruan, C, Chen, Q, Chen, X, Guo, Q, Sun, T, Cheng, J & Jiang, C 2018, 'Enhanced bioreduction-responsive diselenide-based dimeric prodrug nanoparticles for triple negative breast cancer therapy', Theranostics, vol. 8, no. 18, pp. 4884-4897. https://doi.org/10.7150/thno.27581
He, Xi ; Zhang, Jinxiao ; Li, Chao ; Zhang, Yu ; Lu, Yifei ; Zhang, Yujie ; Liu, Lisha ; Ruan, Chunhui ; Chen, Qinjun ; Chen, Xinli ; Guo, Qin ; Sun, Tao ; Cheng, Jianjun ; Jiang, Chen. / Enhanced bioreduction-responsive diselenide-based dimeric prodrug nanoparticles for triple negative breast cancer therapy. In: Theranostics. 2018 ; Vol. 8, No. 18. pp. 4884-4897.
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AU - Zhang, Yujie

AU - Liu, Lisha

AU - Ruan, Chunhui

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AB - Efficient drug accumulation in tumor is essential for chemotherapy. We developed redox-responsive diselenide-based high-loading prodrug nanoparticles (NPs) for targeted triple negative breast cancer (TNBC) treatment. Method: Redox-responsive diselenide bond (Se-Se) containing dimeric prodrug (PTXD-Se) was synthesized and co-precipitated with TNBC-targeting amphiphilic copolymers to form ultra-stable NPs (uPA-PTXD NPs). The drug loading capacity and redox-responsive drug release behavior were studied. TNBC targeting effect and anti-tumor effect were also evaluated in vitro and in vivo. Results: On-demand designed paclitaxel dimeric prodrug could co-precipitate with amphiphilic copolymers to form ultra-stable uPA-PTXD NPs with high drug loading capacity. Diselenide bond (Se-Se) in uPA-PTXD NPs could be selectively cleaved by abnormally high reduced potential in tumor microenvironment, releasing prototype drug, thus contributing to improved anti-cancer efficacy. Endowed with TNBC-targeting ligand uPA peptide, uPA-PTXD NPs exhibited reduced systemic toxicity and enhanced drug accumulation in TNBC lesions, thus showed significant anti-tumor efficacy both in vitro and in vivo. Conclusion: The comprehensive advantage of high drug loading, redox-controlled drug release and targeted tumor accumulation suggests uPA-PTXD NPs as a highly promising strategy for effective TNBC treatment.

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