2. Academic Validation
  3. A cathepsin B/GSH dual-responsive fluorinated peptide for effective siRNA delivery to cancer cells

A cathepsin B/GSH dual-responsive fluorinated peptide for effective siRNA delivery to cancer cells

  • Bioorg Chem. 2023 Jun:135:106485. doi: 10.1016/j.bioorg.2023.106485.
Zhen Shi 1,  Yuhan Yang 1,  Ziyang Guo 1,  Shun Feng 1,  Yu Wan 2
Affiliations

Affiliations

  • 1 Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
  • 2 Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China. Electronic address: [email protected].
PMID: 36963370 DOI: 10.1016/j.bioorg.2023.106485
Abstract

Small interfering RNA (siRNA) can be exploited to silence specific genes associated with Cancer development, and successful siRNA therapy is highly dependent on the efficiency of the siRNA delivery vector. Herein, a well-designed novel redox- and enzyme-responsive fluorinated polyarginine (PFC-PR) was developed to be used as an anti-cancer siRNA carrier. The multiple guanidine groups could provide positive charges and bind with siRNA efficiently, and further fluorination modification enhanced the interaction with siRNA, resulting in a more stable PFC-PR/siRNA nanocomplex, improving serum tolerance, and promoting cellular uptake and endosome escape. Meanwhile, the PFC-PR was responsive to overexpressed Cathepsin B and high levels of glutathione in Cancer cells, conferring its ability to enhance siRNA release within Cancer cells and making it cancer-targeting. Consequently, PFC-PR showed good biocompatibility and high gene silencing efficiency, which could inhibit Cancer cell growth when delivered the siRNA targeting vascular endothelial growth factor, suggesting that it can be potentially used for anti-cancer gene therapy applications.

Keywords

Fluorination; Peptide; Stimuli-responsive; siRNA delivery.

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