Edible and cation-free kiwi fruit derived vesicles mediated EGFR-targeted siRNA delivery to inhibit multidrug resistant lung cancer
Abstract Clinically, activated EGFR mutation associated chemo-drugs resistance has severely threaten NSCLC patients. Nanoparticle based small interfering RNA (siRNA) therapy representing another promising alternative by silencing specific gene while still suffered from charge associated toxicity, st...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-023-01766-w |
| _version_ | 1811165703201357824 |
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| author | Haoying Huang Xiaohan Yi Qingyun Wei Mengyuan Li Xueting Cai Yan Lv Ling Weng Yujie Mao Weiwei Fan Mengmeng Zhao Zhongpei Weng Qing Zhao Kewei Zhao Meng Cao Jing Chen Peng Cao |
| author_facet | Haoying Huang Xiaohan Yi Qingyun Wei Mengyuan Li Xueting Cai Yan Lv Ling Weng Yujie Mao Weiwei Fan Mengmeng Zhao Zhongpei Weng Qing Zhao Kewei Zhao Meng Cao Jing Chen Peng Cao |
| author_sort | Haoying Huang |
| collection | DOAJ |
| description | Abstract Clinically, activated EGFR mutation associated chemo-drugs resistance has severely threaten NSCLC patients. Nanoparticle based small interfering RNA (siRNA) therapy representing another promising alternative by silencing specific gene while still suffered from charge associated toxicity, strong immunogenicity and poor targetability. Herein, we reported a novel EGFR-mutant NSCLC therapy relying on edible and cation-free kiwi-derived extracellular vesicles (KEVs), which showed sevenfold enhancement of safe dosage compared with widely used cationic liposomes and could be further loaded with Signal Transducer and Activator of Transcription 3 interfering RNA (siSTAT3). siSTAT3 loaded KEVs (STAT3/KEVs) could be easily endowed with EGFR targeting ability (STAT3/EKEVs) and fluorescence by surface modification with tailor-making aptamer through hydrophobic interaction. STAT3/EKEVs with a controlled size of 186 nm displayed excellent stability, high specificity and good cytotoxicity towards EGFR over-expressing and mutant PC9-GR4-AZD1 cells. Intriguingly, the systemic administration of STAT3/EKEVs significantly suppressed subcutaneous PC9-GR4-AZD1 tumor xenografts in nude mice by STAT3 mediated apoptosis. This safe and robust KEVs has emerged as the next generation of gene delivery platform for NSCLC therapy after multiple drug-resistance. Graphical Abstract |
| first_indexed | 2024-04-10T15:42:04Z |
| format | Article |
| id | doaj.art-70d7edf95a1743eba2f567191b4077e6 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-10T15:42:04Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-70d7edf95a1743eba2f567191b4077e62023-02-12T12:21:30ZengBMCJournal of Nanobiotechnology1477-31552023-02-0121111410.1186/s12951-023-01766-wEdible and cation-free kiwi fruit derived vesicles mediated EGFR-targeted siRNA delivery to inhibit multidrug resistant lung cancerHaoying Huang0Xiaohan Yi1Qingyun Wei2Mengyuan Li3Xueting Cai4Yan Lv5Ling Weng6Yujie Mao7Weiwei Fan8Mengmeng Zhao9Zhongpei Weng10Qing Zhao11Kewei Zhao12Meng Cao13Jing Chen14Peng Cao15School of Pharmacy, Nanjing University of Chinese MedicineSchool of Pharmacy, Nanjing University of Chinese MedicineSchool of Pharmacy, Nanjing University of Chinese MedicineSchool of Pharmacy, Nanjing University of Chinese MedicineSchool of Pharmacy, Nanjing University of Chinese MedicineSchool of Pharmacy, Nanjing University of Chinese MedicineSchool of Pharmacy, Nanjing University of Chinese MedicineSchool of Pharmacy, Nanjing University of Chinese MedicineAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineSchool of Pharmacy, Nanjing University of Chinese MedicineGaoyou Hospital of Traditional Chinese MedicineGuangzhou Key Laboratory of Chinese Medicine Research on Prevention and Treatment of Osteoporosis, The Third Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou Key Laboratory of Chinese Medicine Research on Prevention and Treatment of Osteoporosis, The Third Affiliated Hospital of Guangzhou University of Chinese MedicineSchool of Pharmacy, Nanjing University of Chinese MedicineSchool of Pharmacy, Nanjing University of Chinese MedicineSchool of Pharmacy, Nanjing University of Chinese MedicineAbstract Clinically, activated EGFR mutation associated chemo-drugs resistance has severely threaten NSCLC patients. Nanoparticle based small interfering RNA (siRNA) therapy representing another promising alternative by silencing specific gene while still suffered from charge associated toxicity, strong immunogenicity and poor targetability. Herein, we reported a novel EGFR-mutant NSCLC therapy relying on edible and cation-free kiwi-derived extracellular vesicles (KEVs), which showed sevenfold enhancement of safe dosage compared with widely used cationic liposomes and could be further loaded with Signal Transducer and Activator of Transcription 3 interfering RNA (siSTAT3). siSTAT3 loaded KEVs (STAT3/KEVs) could be easily endowed with EGFR targeting ability (STAT3/EKEVs) and fluorescence by surface modification with tailor-making aptamer through hydrophobic interaction. STAT3/EKEVs with a controlled size of 186 nm displayed excellent stability, high specificity and good cytotoxicity towards EGFR over-expressing and mutant PC9-GR4-AZD1 cells. Intriguingly, the systemic administration of STAT3/EKEVs significantly suppressed subcutaneous PC9-GR4-AZD1 tumor xenografts in nude mice by STAT3 mediated apoptosis. This safe and robust KEVs has emerged as the next generation of gene delivery platform for NSCLC therapy after multiple drug-resistance. Graphical Abstracthttps://doi.org/10.1186/s12951-023-01766-wKiwiExtracellular vesiclesRNA aptamersTargeted siRNA deliveryNon-small cell lung cancerDrug resistance |
| spellingShingle | Haoying Huang Xiaohan Yi Qingyun Wei Mengyuan Li Xueting Cai Yan Lv Ling Weng Yujie Mao Weiwei Fan Mengmeng Zhao Zhongpei Weng Qing Zhao Kewei Zhao Meng Cao Jing Chen Peng Cao Edible and cation-free kiwi fruit derived vesicles mediated EGFR-targeted siRNA delivery to inhibit multidrug resistant lung cancer Journal of Nanobiotechnology Kiwi Extracellular vesicles RNA aptamers Targeted siRNA delivery Non-small cell lung cancer Drug resistance |
| title | Edible and cation-free kiwi fruit derived vesicles mediated EGFR-targeted siRNA delivery to inhibit multidrug resistant lung cancer |
| title_full | Edible and cation-free kiwi fruit derived vesicles mediated EGFR-targeted siRNA delivery to inhibit multidrug resistant lung cancer |
| title_fullStr | Edible and cation-free kiwi fruit derived vesicles mediated EGFR-targeted siRNA delivery to inhibit multidrug resistant lung cancer |
| title_full_unstemmed | Edible and cation-free kiwi fruit derived vesicles mediated EGFR-targeted siRNA delivery to inhibit multidrug resistant lung cancer |
| title_short | Edible and cation-free kiwi fruit derived vesicles mediated EGFR-targeted siRNA delivery to inhibit multidrug resistant lung cancer |
| title_sort | edible and cation free kiwi fruit derived vesicles mediated egfr targeted sirna delivery to inhibit multidrug resistant lung cancer |
| topic | Kiwi Extracellular vesicles RNA aptamers Targeted siRNA delivery Non-small cell lung cancer Drug resistance |
| url | https://doi.org/10.1186/s12951-023-01766-w |
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