Tumor targeting and microenvironment-responsive multifunctional fusion protein for pro-apoptotic peptide delivery
| Autor: | Dingkang Liu, Chen Ye, Qun Wang, Jun Yin, Shan Hou, Lichen Bao, Xiangdong Gao, Wenbing Yao, Yali Yue |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Recombinant Fusion Proteins Mice Nude Antineoplastic Agents Apoptosis Peptide Cell-Penetrating Peptides Matrix metalloproteinase 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Protein Domains In vivo Neoplasms Tumor Microenvironment Animals Humans Molecular Targeted Therapy Cell Proliferation Membrane Potential Mitochondrial chemistry.chemical_classification Drug Carriers Mice Inbred BALB C Polyglutamic acid Hep G2 Cells Xenograft Model Antitumor Assays Fusion protein Peptide Fragments In vitro Mitochondria Cell biology 030104 developmental biology Polyglutamic Acid Oncology chemistry 030220 oncology & carcinogenesis MCF-7 Cells Cell-penetrating peptide Matrix Metalloproteinase 2 Female Signal Transduction |
| Zdroj: | Cancer Letters. 452:38-50 |
| ISSN: | 0304-3835 |
| DOI: | 10.1016/j.canlet.2019.03.016 |
| Popis: | The great therapeutic potential of peptides has not yet been achieved, mainly due to their remarkably short in vivo half-life. Although conjugation to macromolecules has been an effective way of improving protein in vivo half-life, the steric hindrance of macromolecules usually reduces the in vivo efficacy of peptides. Here we report a complex delivery system made from PsTag polypeptide, polyglutamic acid chain, matrix metalloproteinase 2 (MMP2)-degradable domain and cationic cell penetrating peptide for anticancer peptide delivery. Clear evidence was shown in vitro and in vivo to demonstrate that this multifunctional protein fusing a pro-apoptotic KLAKLAKKLAKLAK (KLA), named PAK, can increase circulation time in blood, enhance accumulation at tumor sites, eliminate the PsTag domain and the polyanionic sequence when triggered by tumor overexpressing MMP2, and then expose the cell penetrating peptide to realize the potent cellular uptake of KLA. Treatment of tumor-bearing mice with PAK could markedly induce tumor cells apoptosis and inhibit tumor growth, with no significant adverse effects. These results suggest our fusion protein can be a potential delivery system for peptide delivery in cancer treatments. |
| Databáze: | OpenAIRE |
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