A new NCL-targeting aptamer-drug conjugate as a promising therapy against esophageal cancer
Abstract Esophageal cancer (EC) is one of the most common highly malignant tumors of the digestive system, with a poor prognosis under current treatment regimens. Nucleolin (NCL) is overexpressed in many tumors, and drugs specifically targeting NCL may offer a promising strategy for treating esophag...
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| Format: | Article |
| Language: | English |
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BMC
2025-01-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03127-1 |
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| author | Xue Zheng Ying Wang Huaiyu Duan Junqi Hou Shiming He |
| author_facet | Xue Zheng Ying Wang Huaiyu Duan Junqi Hou Shiming He |
| author_sort | Xue Zheng |
| collection | DOAJ |
| description | Abstract Esophageal cancer (EC) is one of the most common highly malignant tumors of the digestive system, with a poor prognosis under current treatment regimens. Nucleolin (NCL) is overexpressed in many tumors, and drugs specifically targeting NCL may offer a promising strategy for treating esophageal cancer. Here, we designed and prepared a novel aptamer-conjugated drug targeting NCL by AS1411 aptamer-human serum albumin (HSA)-the apoprotein of lidamycin (LDP)-active enediyne chromophore (AE), in order to achieve targeted treatment of esophageal cancer. The experimental results revealed that AS1411-HSA-LDP effectively binds to esophageal cancer cells and could be efficiently internalized by esophageal cancer cells. In the KYSE520 xenograft tumor nude mouse model, AS1411-HSA-LDP could be targeted and enriched in the tumor location for a long time. AS1411-HSA-LDP-AE exhibited a strong cell-killing activity in esophageal cancer cells, inhibited cell migration and invasion, and induced cell apoptosis. The animal studies confirmed that AS1411-HSA-LDP-AE exhibited a strong anti-tumor effect. These findings suggested that the novel NCL-targeting aptamer-drug conjugate constructed based on lidamycin exhibited a strong anti-tumor effect, providing a promising strategy for the targeted treatment of esophageal cancer. |
| format | Article |
| id | doaj-art-931b4ac6b2e1472d9c4420c012124d26 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-931b4ac6b2e1472d9c4420c012124d262025-02-02T12:41:10ZengBMCJournal of Nanobiotechnology1477-31552025-01-0123112310.1186/s12951-025-03127-1A new NCL-targeting aptamer-drug conjugate as a promising therapy against esophageal cancerXue Zheng0Ying Wang1Huaiyu Duan2Junqi Hou3Shiming He4School of Integrated Chinese and Western Medicine, Anhui University of Chinese MedicineInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Peking Union Medical CollegeSchool of Integrated Chinese and Western Medicine, Anhui University of Chinese MedicineSchool of Integrated Chinese and Western Medicine, Anhui University of Chinese MedicineSchool of Integrated Chinese and Western Medicine, Anhui University of Chinese MedicineAbstract Esophageal cancer (EC) is one of the most common highly malignant tumors of the digestive system, with a poor prognosis under current treatment regimens. Nucleolin (NCL) is overexpressed in many tumors, and drugs specifically targeting NCL may offer a promising strategy for treating esophageal cancer. Here, we designed and prepared a novel aptamer-conjugated drug targeting NCL by AS1411 aptamer-human serum albumin (HSA)-the apoprotein of lidamycin (LDP)-active enediyne chromophore (AE), in order to achieve targeted treatment of esophageal cancer. The experimental results revealed that AS1411-HSA-LDP effectively binds to esophageal cancer cells and could be efficiently internalized by esophageal cancer cells. In the KYSE520 xenograft tumor nude mouse model, AS1411-HSA-LDP could be targeted and enriched in the tumor location for a long time. AS1411-HSA-LDP-AE exhibited a strong cell-killing activity in esophageal cancer cells, inhibited cell migration and invasion, and induced cell apoptosis. The animal studies confirmed that AS1411-HSA-LDP-AE exhibited a strong anti-tumor effect. These findings suggested that the novel NCL-targeting aptamer-drug conjugate constructed based on lidamycin exhibited a strong anti-tumor effect, providing a promising strategy for the targeted treatment of esophageal cancer.https://doi.org/10.1186/s12951-025-03127-1Esophageal cancerLidamycinAS1411Human serum albumin |
| spellingShingle | Xue Zheng Ying Wang Huaiyu Duan Junqi Hou Shiming He A new NCL-targeting aptamer-drug conjugate as a promising therapy against esophageal cancer Journal of Nanobiotechnology Esophageal cancer Lidamycin AS1411 Human serum albumin |
| title | A new NCL-targeting aptamer-drug conjugate as a promising therapy against esophageal cancer |
| title_full | A new NCL-targeting aptamer-drug conjugate as a promising therapy against esophageal cancer |
| title_fullStr | A new NCL-targeting aptamer-drug conjugate as a promising therapy against esophageal cancer |
| title_full_unstemmed | A new NCL-targeting aptamer-drug conjugate as a promising therapy against esophageal cancer |
| title_short | A new NCL-targeting aptamer-drug conjugate as a promising therapy against esophageal cancer |
| title_sort | new ncl targeting aptamer drug conjugate as a promising therapy against esophageal cancer |
| topic | Esophageal cancer Lidamycin AS1411 Human serum albumin |
| url | https://doi.org/10.1186/s12951-025-03127-1 |
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