2. Academic Validation
  3. Benzaldehyde-tethered fluorous tags for cytosolic delivery of bioactive peptides

Benzaldehyde-tethered fluorous tags for cytosolic delivery of bioactive peptides

  • J Control Release. 2022 Oct 7;351:703-712. doi: 10.1016/j.jconrel.2022.09.064.
Guangyu Rong 1,  Changping Wang 2,  Junfei Hu 3,  Yiwen Li 4,  Yiyun Cheng 5
Affiliations

Affiliations

  • 1 Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, PR China; South China Advanced Institute for Soft Matter Science and Technology, Guangdong Provincial Key Laboratory of Functional and Intelligent Hybrid Materials and Devices, School of Emergent Soft Matter, South China University of Technology, Guangzhou 510640, PR China.
  • 2 South China Advanced Institute for Soft Matter Science and Technology, Guangdong Provincial Key Laboratory of Functional and Intelligent Hybrid Materials and Devices, School of Emergent Soft Matter, South China University of Technology, Guangzhou 510640, PR China.
  • 3 College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, PR China.
  • 4 College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, PR China. Electronic address: ywli@scu.edu.cn.
  • 5 Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, PR China; South China Advanced Institute for Soft Matter Science and Technology, Guangdong Provincial Key Laboratory of Functional and Intelligent Hybrid Materials and Devices, School of Emergent Soft Matter, South China University of Technology, Guangzhou 510640, PR China. Electronic address: yycheng@mail.ustc.edu.cn.
PMID: 36202150 DOI: 10.1016/j.jconrel.2022.09.064
Abstract

Development of intracellular delivery systems for bioactive Peptides remains challenging. Herein, we report a facile strategy to address this issue by conjugating Peptides with benzaldehyde-tethered fluorous tags to generate dynamic peptide amphiphiles via a hydrazone bond for efficient cytosolic delivery. Those dynamic peptide fluoroamphiphiles could self-assemble into nanoparticles that readily cross the cell membrane. Using this strategy, several bioactive Peptides were efficiently internalized by Cancer cells and released into the cytosol to exert their biological functions, which showed much higher efficacies than non-fluorous lipids and cell penetrating peptide decorated Peptides. Moreover, the fluorous tagged proapoptotic peptide was able to efficiently inhibit tumor growth in vivo. This report provides a new family of fluorous tags based on benzaldehyde for efficient cytosolic peptide delivery.

Keywords

Amphiphile; Cytosolic peptide delivery; Fluorous tag; Peptide; Supramolecular assembly.

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