Aptamer-Equipped Protamine Nanomedicine for Precision Lymphoma Therapy
Anaplastic large cell lymphoma (ALCL) is the most common T-cell lymphoma in children. ALCL cells characteristically express surface CD30 molecules and carry the pathogenic ALK oncogene, both of which are diagnostic biomarkers and are also potential therapeutic targets. For precision therapy, we repo...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-03-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/12/4/780 |
| _version_ | 1797761273660702720 |
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| author | Zihua Zeng Ching-Hsuan Tung Youli Zu |
| author_facet | Zihua Zeng Ching-Hsuan Tung Youli Zu |
| author_sort | Zihua Zeng |
| collection | DOAJ |
| description | Anaplastic large cell lymphoma (ALCL) is the most common T-cell lymphoma in children. ALCL cells characteristically express surface CD30 molecules and carry the pathogenic ALK oncogene, both of which are diagnostic biomarkers and are also potential therapeutic targets. For precision therapy, we report herein a protamine nanomedicine incorporated with oligonucleotide aptamers to selectively target lymphoma cells, a dsDNA/drug payload to efficiently kill targeted cells, and an siRNA to specifically silence ALK oncogenes. The aptamer-equipped protamine nanomedicine was simply fabricated through a non-covalent charge-force reaction. The products had uniform structure morphology under an electron microscope and a peak diameter of 103 nm by dynamic light scattering measurement. Additionally, flow cytometry analysis demonstrated that under CD30 aptamer guidance, the protamine nanomedicine specifically bound to lymphoma cells, but did not react to off-target cells in control experiments. Moreover, specific cell targeting and intracellular delivery of the nanomedicine were also validated by electron and confocal microscopy. Finally, functional studies demonstrated that, through combined cell-selective chemotherapy using a drug payload and oncogene-specific gene therapy using an siRNA, the protamine nanomedicine effectively killed lymphoma cells with little toxicity to off-target cells, indicating its potential for precision therapy. |
| first_indexed | 2024-03-12T19:11:36Z |
| format | Article |
| id | doaj.art-e555d5ca351a4e31af219efdc7963f17 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T19:11:36Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-e555d5ca351a4e31af219efdc7963f172023-08-02T05:55:48ZengMDPI AGCancers2072-66942020-03-0112478010.3390/cancers12040780cancers12040780Aptamer-Equipped Protamine Nanomedicine for Precision Lymphoma TherapyZihua Zeng0Ching-Hsuan Tung1Youli Zu2Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Cancer Pathology Research Laboratory, Houston Methodist Research Institute, Houston TX 77030, USAMolecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medical College, New York, NY 10021, USADepartment of Pathology and Genomic Medicine, Houston Methodist Hospital, Cancer Pathology Research Laboratory, Houston Methodist Research Institute, Houston TX 77030, USAAnaplastic large cell lymphoma (ALCL) is the most common T-cell lymphoma in children. ALCL cells characteristically express surface CD30 molecules and carry the pathogenic ALK oncogene, both of which are diagnostic biomarkers and are also potential therapeutic targets. For precision therapy, we report herein a protamine nanomedicine incorporated with oligonucleotide aptamers to selectively target lymphoma cells, a dsDNA/drug payload to efficiently kill targeted cells, and an siRNA to specifically silence ALK oncogenes. The aptamer-equipped protamine nanomedicine was simply fabricated through a non-covalent charge-force reaction. The products had uniform structure morphology under an electron microscope and a peak diameter of 103 nm by dynamic light scattering measurement. Additionally, flow cytometry analysis demonstrated that under CD30 aptamer guidance, the protamine nanomedicine specifically bound to lymphoma cells, but did not react to off-target cells in control experiments. Moreover, specific cell targeting and intracellular delivery of the nanomedicine were also validated by electron and confocal microscopy. Finally, functional studies demonstrated that, through combined cell-selective chemotherapy using a drug payload and oncogene-specific gene therapy using an siRNA, the protamine nanomedicine effectively killed lymphoma cells with little toxicity to off-target cells, indicating its potential for precision therapy.https://www.mdpi.com/2072-6694/12/4/780aptamerlymphomaprecision therapyprotamine nanomedicinetargeting delivery. |
| spellingShingle | Zihua Zeng Ching-Hsuan Tung Youli Zu Aptamer-Equipped Protamine Nanomedicine for Precision Lymphoma Therapy Cancers aptamer lymphoma precision therapy protamine nanomedicine targeting delivery. |
| title | Aptamer-Equipped Protamine Nanomedicine for Precision Lymphoma Therapy |
| title_full | Aptamer-Equipped Protamine Nanomedicine for Precision Lymphoma Therapy |
| title_fullStr | Aptamer-Equipped Protamine Nanomedicine for Precision Lymphoma Therapy |
| title_full_unstemmed | Aptamer-Equipped Protamine Nanomedicine for Precision Lymphoma Therapy |
| title_short | Aptamer-Equipped Protamine Nanomedicine for Precision Lymphoma Therapy |
| title_sort | aptamer equipped protamine nanomedicine for precision lymphoma therapy |
| topic | aptamer lymphoma precision therapy protamine nanomedicine targeting delivery. |
| url | https://www.mdpi.com/2072-6694/12/4/780 |
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