https://scholars.lib.ntu.edu.tw/handle/123456789/531091
Title: | Study of the intracellular delivery mechanism of a pH-sensitive peptide modified with enhanced green fluorescent protein | Authors: | Chiu P.-C. Hsieh P.-Y. Kang J.-W. Chang P.-H. LI-JIUAN SHEN |
Keywords: | Cell-penetrating peptide (CPP); HBHAc; intracellular protein delivery; mechanism; pH sensitive | Issue Date: | 2020 | Journal Volume: | 28 | Journal Issue: | 4 | Start page/Pages: | 408-418 | Source: | Journal of Drug Targeting | Abstract: | The targeted delivery of therapeutic agents is a promising approach to enhance the efficacy and reduce the toxicity of cancer treatments. Understanding the intracellular endocytic mechanisms of a cell penetrating peptide (CPP) in an acidic environment is important for targeted delivery of macromolecules to tumours. In this study, we constructed a pH-sensitive CPP-based delivery system for the intracellular delivery of macromolecules. A pH-sensitive CPP, HBHAc, was fused with a model protein, enhanced green fluorescent protein (EGFP), through recombinant DNA technology. We found that is essential that negatively charged proteoglycans on the cell surface interact with HBHAc-EGFP prior to the cellular uptake of HBHAc-EGFP. The uptake was significantly restricted at 4 °C under pH conditions of both 6.5 and 7.5. The increased positive charge of HBHAc-EGFP under the acidic condition leads to a pH-dependent cellular uptake, and we observed that the internalisation of HBHAc-EGFP was significantly higher at pH 6.5 than at pH 7.5 (p <.05). Thus, with pH-sensitive activity, HBHAc is expected to improve tumour-targeted intracellular protein delivery. Moreover, our findings provide a new insight that the endocytic pathway may change under different pH conditions and suggest that this unique phenomenon benefits pH-sensitive drug delivery for tumour therapy. ? 2019, ? 2019 Informa UK Limited, trading as Taylor & Francis Group. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/531091 | ISSN: | 1061186X | DOI: | 10.1080/1061186X.2019.1669041 | SDG/Keyword: | cell penetrating peptide; cell protein; enhanced green fluorescent protein; fusion protein; heparin binding hemagglutinin adhesion protein; proteoglycan; recombinant protein; unclassified drug; cell penetrating peptide; enhanced green fluorescent protein; green fluorescent protein; acidity; Article; cancer therapy; cell surface; cell viability; controlled study; drug delivery system; endocytosis; human; human cell; internalization; macromolecule; pH; priority journal; protein modification; recombinant DNA technology; cell membrane; cytoplasm; drug delivery system; drug effect; Hep-G2 cell line; metabolism; neoplasm; pH; procedures; signal transduction; tumor cell line; Cell Line, Tumor; Cell Membrane; Cell-Penetrating Peptides; Cytoplasm; Drug Delivery Systems; Endocytosis; Green Fluorescent Proteins; Hep G2 Cells; Humans; Hydrogen-Ion Concentration; Neoplasms; Signal Transduction |
Appears in Collections: | 臨床藥學研究所 |
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