The mirrored cationic peptide as miRNA vehicle for efficient lung cancer therapy
Abstract Gene therapy has emerged as a potential approach for lung cancer therapy. However, the application of gene therapy is still limited by their properties, such as low specificity to the cancer cells, negatively charged groups, short systemic circulation time, and rapid degradation by nuclease...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-08-01
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| Series: | MedComm |
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| Online Access: | https://doi.org/10.1002/mco2.273 |
| _version_ | 1827825210552745984 |
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| author | Wenyan Xu Lingran Du Lina Yu Huiyu Cen Fangyu Lin Siran Wang Zhixiong Ruan Zhongxiao Lin Xin Zhang Na Zhou Jishuo Chang Xiyong Yu Lingmin Zhang Lu Liang |
| author_facet | Wenyan Xu Lingran Du Lina Yu Huiyu Cen Fangyu Lin Siran Wang Zhixiong Ruan Zhongxiao Lin Xin Zhang Na Zhou Jishuo Chang Xiyong Yu Lingmin Zhang Lu Liang |
| author_sort | Wenyan Xu |
| collection | DOAJ |
| description | Abstract Gene therapy has emerged as a potential approach for lung cancer therapy. However, the application of gene therapy is still limited by their properties, such as low specificity to the cancer cells, negatively charged groups, short systemic circulation time, and rapid degradation by nucleases. The progression of lung adenocarcinoma (LUAD) can be promoted through the methylation process of miR‐148a‐3p promoter, as confirmed by our previous research. In the current study, we are the first to design a mirrored Arg‐Gly‐Asp (RGD)‐modified cationic peptide (RD24) as a microRNA (miRNA) vehicle, which enabled to pack the miRNA (miR‐148a‐3p) efficiently and generate RD24/miR‐148a‐3p nanoparticles (RPRIN) by self‐assembling. RPRIN exhibited a high transfection efficiency in lung cancer cells via the conjugation between RGD and integrins on the surface of lung cancer cells. Furthermore, RD24 showed matrix metallopeptidase 2 (MMP2) responsiveness, which improved lung cancer cell inhibition induced by the miRNA intracellularly. In addition, RPRIN exhibits several advantages, such as prolonged circulation duration, reduced toxicity, and immune escape. Experiments conducted both in vitro and in vivo revealed that RPRIN effectively suppressed the growth and progression of lung cancer. Thus, the mirrored RGD‐modified cationic peptide showed great potential in transducing miRNA for lung cancer therapy. |
| first_indexed | 2024-03-12T02:38:53Z |
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| id | doaj.art-fe234a53a96b4dbcb7748a05d1b4a2f0 |
| institution | Directory Open Access Journal |
| issn | 2688-2663 |
| language | English |
| last_indexed | 2024-03-12T02:38:53Z |
| publishDate | 2023-08-01 |
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| series | MedComm |
| spelling | doaj.art-fe234a53a96b4dbcb7748a05d1b4a2f02023-09-04T11:20:36ZengWileyMedComm2688-26632023-08-0144n/an/a10.1002/mco2.273The mirrored cationic peptide as miRNA vehicle for efficient lung cancer therapyWenyan Xu0Lingran Du1Lina Yu2Huiyu Cen3Fangyu Lin4Siran Wang5Zhixiong Ruan6Zhongxiao Lin7Xin Zhang8Na Zhou9Jishuo Chang10Xiyong Yu11Lingmin Zhang12Lu Liang13Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital Guangzhou Medical University Guangzhou PR ChinaGuangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital Guangzhou Medical University Guangzhou PR ChinaGuangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital Guangzhou Medical University Guangzhou PR ChinaGuangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital Guangzhou Medical University Guangzhou PR ChinaDepartment of Ophthalmology Emory University Atlanta Georgia USAGuangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital Guangzhou Medical University Guangzhou PR ChinaGuangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital Guangzhou Medical University Guangzhou PR ChinaGuangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital Guangzhou Medical University Guangzhou PR ChinaState Key Laboratory of Quality Research in Chinese Medicine Macau University of Science and Technology Avenida Wailong Taipa Macau PR ChinaState Key Laboratory of Quality Research in Chinese Medicine Macau University of Science and Technology Avenida Wailong Taipa Macau PR ChinaGuangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital Guangzhou Medical University Guangzhou PR ChinaGuangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital Guangzhou Medical University Guangzhou PR ChinaGuangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital Guangzhou Medical University Guangzhou PR ChinaGuangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital Guangzhou Medical University Guangzhou PR ChinaAbstract Gene therapy has emerged as a potential approach for lung cancer therapy. However, the application of gene therapy is still limited by their properties, such as low specificity to the cancer cells, negatively charged groups, short systemic circulation time, and rapid degradation by nucleases. The progression of lung adenocarcinoma (LUAD) can be promoted through the methylation process of miR‐148a‐3p promoter, as confirmed by our previous research. In the current study, we are the first to design a mirrored Arg‐Gly‐Asp (RGD)‐modified cationic peptide (RD24) as a microRNA (miRNA) vehicle, which enabled to pack the miRNA (miR‐148a‐3p) efficiently and generate RD24/miR‐148a‐3p nanoparticles (RPRIN) by self‐assembling. RPRIN exhibited a high transfection efficiency in lung cancer cells via the conjugation between RGD and integrins on the surface of lung cancer cells. Furthermore, RD24 showed matrix metallopeptidase 2 (MMP2) responsiveness, which improved lung cancer cell inhibition induced by the miRNA intracellularly. In addition, RPRIN exhibits several advantages, such as prolonged circulation duration, reduced toxicity, and immune escape. Experiments conducted both in vitro and in vivo revealed that RPRIN effectively suppressed the growth and progression of lung cancer. Thus, the mirrored RGD‐modified cationic peptide showed great potential in transducing miRNA for lung cancer therapy.https://doi.org/10.1002/mco2.273lung cancermicroRNAMMP2‐sensitive peptideRGD |
| spellingShingle | Wenyan Xu Lingran Du Lina Yu Huiyu Cen Fangyu Lin Siran Wang Zhixiong Ruan Zhongxiao Lin Xin Zhang Na Zhou Jishuo Chang Xiyong Yu Lingmin Zhang Lu Liang The mirrored cationic peptide as miRNA vehicle for efficient lung cancer therapy MedComm lung cancer microRNA MMP2‐sensitive peptide RGD |
| title | The mirrored cationic peptide as miRNA vehicle for efficient lung cancer therapy |
| title_full | The mirrored cationic peptide as miRNA vehicle for efficient lung cancer therapy |
| title_fullStr | The mirrored cationic peptide as miRNA vehicle for efficient lung cancer therapy |
| title_full_unstemmed | The mirrored cationic peptide as miRNA vehicle for efficient lung cancer therapy |
| title_short | The mirrored cationic peptide as miRNA vehicle for efficient lung cancer therapy |
| title_sort | mirrored cationic peptide as mirna vehicle for efficient lung cancer therapy |
| topic | lung cancer microRNA MMP2‐sensitive peptide RGD |
| url | https://doi.org/10.1002/mco2.273 |
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