2. Academic Validation
  3. Suicide gene delivery by morphology-adaptable enantiomeric peptide assemblies for combined ovarian cancer therapy

Suicide gene delivery by morphology-adaptable enantiomeric peptide assemblies for combined ovarian cancer therapy

  • Acta Biomater. 2023 Dec 18:S1742-7061(23)00724-9. doi: 10.1016/j.actbio.2023.12.020.
Na Song 1,  Zhe Sun 2,  Bo Wang 3,  Xin Liu 4,  Binbin Hu 4,  Ninglin Chen 5,  Sihe Zhang 6,  Zhilin Yu 7
Affiliations

Affiliations

  • 1 Ministry of Education Key Laboratory of Functional Polymer Materials, State Key Laboratory of Medicinal Chemical Biology, Institute of Polymer Chemistry, College of Chemistry, Nankai University, 94 Weijin Road, Tianjin 300071, China; Shandong Provincial Engineering Laboratory of Novel Pharmaceutical Excipients and Controlled Release Preparations, College of Medicine and Nursing, Dezhou University, China.
  • 2 School of Life Sciences, Tianjin University, Weijin Road 92, Tianjin 300072, China.
  • 3 Department of Cell Biology, School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China.
  • 4 Ministry of Education Key Laboratory of Functional Polymer Materials, State Key Laboratory of Medicinal Chemical Biology, Institute of Polymer Chemistry, College of Chemistry, Nankai University, 94 Weijin Road, Tianjin 300071, China.
  • 5 Ministry of Education Key Laboratory of Functional Polymer Materials, State Key Laboratory of Medicinal Chemical Biology, Institute of Polymer Chemistry, College of Chemistry, Nankai University, 94 Weijin Road, Tianjin 300071, China; The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, 36 Lushan Road, Changsha, Hunan 410000, China.
  • 6 Department of Cell Biology, School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China. Electronic address: sihezhang@nankai.edu.cn.
  • 7 Ministry of Education Key Laboratory of Functional Polymer Materials, State Key Laboratory of Medicinal Chemical Biology, Institute of Polymer Chemistry, College of Chemistry, Nankai University, 94 Weijin Road, Tianjin 300071, China. Electronic address: yzh026@nankai.edu.cn.
PMID: 38122884 DOI: 10.1016/j.actbio.2023.12.020
Abstract

Suicide gene therapy is a promising therapeutic model for ovarian Cancer (OC), while suffering from poor gene delivery and limited therapeutic efficacy. To address this concern, here we reported the GSH-responsive morphology-transformable enantiomeric peptide assemblies as delivering vehicles for suicide genes and co-delivery of paclitaxel (PTX). Connecting a lipid-like amphiphile and a hydrophilic arginine segment through disulfide bonds led to the enantiomeric Peptides. The enantiomeric peptide assemblies are able to simultaneously uptake plasmid DNA (pDNA) and PTX based on electrostatic and hydrophobic interactions. The resulting co-assemblies underwent GSH-responsive disulfide cleavage and thereby promoting their assembly from nanoparticles to nanofibers, leading to the co-release of pDNA and PTX. Cellular and animal studies confirmed the co-delivery of pDNA and PTX into OC cells and the cell Apoptosis by the enantiomeric Peptides. In addition, in vitro and in vivo experiments supported the advanced uptake and cytotoxicity for L-type peptide vehicles by OC cells, and their great potential for OC-imaging, growth-inhibition and apoptosis-induction compared to D-counterpart. Our results demonstrate that the GSH-responsive morphology-transformable chiral peptide assemblies accurately and simultaneously release suicide genes and chemodrugs at tumor sites, thus providing a new strategy for the development of delivering vehicles for suicide gene and establishment of new therapeutic models for ovarian Cancer. STATEMENT OF SIGNIFICANCE: Appropriate delivery carriers are essential for the clinical translation of Cancer gene therapy, including the emerging suicide gene therapy. By combining the advantages of morphological transformable vehicles with the chirality Peptides towards their bioactivity, we developed the GSH-responsive morphology-transformable enantiomeric peptide assemblies as delivering vehicles for suicide genes and co-delivery of paclitaxel. The GSH-responsive assembly of the enantiomeric Peptides allows for precise release of plasmid DNA and paclitaxel in Cancer cells, and promotes the formation of nanofibrils that facilitate gene entering nuclei for transfection. The enantiomeric peptide-based vehicles show the chirality-dependent capability for inducing cell Apoptosis and inhibiting tumor growth. Our findings demonstrate a new strategy for developing therapeutic models for ovarian Cancer.

Keywords

Cancer therapy; Chirality; Drug delivery; Peptides; Stimulus-responsive.

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