Deacetylated-poly-N-acetylglucosamine-folic Acid as a Nanocarrier for Delivering miR-196a Inhibitor to Anticancer Activity
Background: MiR-196a is particularly noticeable in the development of liver cancer. However, the rapid degradation by ribonuclease (RNase) imposes a limit on the miRNA gene therapy applications. Aims: To design a novel gene-targeting nano system for liver cancer treatment. Study Design: Cell cultu...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Galenos Publishing House
2022-01-01
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| Series: | Balkan Medical Journal |
| Online Access: | https://balkanmedicaljournal.org/text.php?lang=en&id=2364 |
| _version_ | 1828014901085339648 |
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| author | Yuxia Hao Xi Li |
| author_facet | Yuxia Hao Xi Li |
| author_sort | Yuxia Hao |
| collection | DOAJ |
| description | Background: MiR-196a is particularly noticeable in the development of liver cancer. However, the rapid degradation by ribonuclease (RNase) imposes a limit on the miRNA gene therapy applications.
Aims: To design a novel gene-targeting nano system for liver cancer treatment.
Study Design: Cell culture study and animal experimentation
Methods: Deacetylated (DEAC)-poly-N-acetylglucosamine (PNAG)-folic acid (FA) was prepared via ethyl (dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide reaction, and miR-196a inhibitor (miR-196a I)/DEAC-PNAG-FA was prepared through self-assembly. The characterization and nucleic acid protection of the self-assembly system were also determined. The biological function and related mechanism of the prepared system were studied at cellular and molecular levels. Mice were established as a xenotransplantation model to evaluate the anticancer capacity of miR-196a I/DEAC-PNAG-FA in vivo.
Results: The morphology of miR-196a I/DEAC-PNAG-FA was uniform, and its particle size was approximately 70–100 nm. A nanocarrier with an N/P ratio of 200:1 can maximize the nucleic acid carrying capacity of the self-assembly system. The nanosystem can protect miRNA from RNase degradation and could be internalized rapidly within 4 h. The self-assembly system significantly enhanced the apoptosis-inducing effect of miR-196a I on HepG2 cells (P = 0.003). Molecular biological analyses confirmed that the apoptosis-inducing effect of the nanosystem was due to the inhibition of miR-196a gene expression in HepG2 cells, which upregulate the expression of pro-apoptotic proteins FOXO1 (P < 0.001), Bax (P < 0.001), Ki67 (P < 0.001), and proliferating cell nuclear antigen (P < 0.001), and inhibit the expression of apoptosis inhibitory protein Bcl-2 (P < 0.001). Moreover, compared with free miR-196a inhibitor or miR-196a I/DEAC-PNAG, miR-196a I/DEAC-PNAG-FA can more effectively inhibit tumor growth in vivo (P = 0.026).
Conclusion: The newly prepared self-assembly targeting system can effectively induce apoptosis and abrogate tumor growth, which may open a new approach for liver cancer treatment. |
| first_indexed | 2024-04-10T10:09:22Z |
| format | Article |
| id | doaj.art-c520cddebb214b4db9140beaac5c9800 |
| institution | Directory Open Access Journal |
| issn | 2146-3123 2146-3131 |
| language | English |
| last_indexed | 2024-04-10T10:09:22Z |
| publishDate | 2022-01-01 |
| publisher | Galenos Publishing House |
| record_format | Article |
| series | Balkan Medical Journal |
| spelling | doaj.art-c520cddebb214b4db9140beaac5c98002023-02-15T16:22:19ZengGalenos Publishing HouseBalkan Medical Journal2146-31232146-31312022-01-01391556510.4274/balkanmedj.galenos.2021.2021-8-62Deacetylated-poly-N-acetylglucosamine-folic Acid as a Nanocarrier for Delivering miR-196a Inhibitor to Anticancer ActivityYuxia Hao0https://orcid.org/0000-0002-6844-6071Xi Li1https://orcid.org/0000-0002-5474-2873Department of Gastroenterology, Shanxi Provincial People’s Hospital, Shanxi, ChinaDepartment of Lymphoma, Shanxi Bethune Hospital, Shanxi, ChinaBackground: MiR-196a is particularly noticeable in the development of liver cancer. However, the rapid degradation by ribonuclease (RNase) imposes a limit on the miRNA gene therapy applications. Aims: To design a novel gene-targeting nano system for liver cancer treatment. Study Design: Cell culture study and animal experimentation Methods: Deacetylated (DEAC)-poly-N-acetylglucosamine (PNAG)-folic acid (FA) was prepared via ethyl (dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide reaction, and miR-196a inhibitor (miR-196a I)/DEAC-PNAG-FA was prepared through self-assembly. The characterization and nucleic acid protection of the self-assembly system were also determined. The biological function and related mechanism of the prepared system were studied at cellular and molecular levels. Mice were established as a xenotransplantation model to evaluate the anticancer capacity of miR-196a I/DEAC-PNAG-FA in vivo. Results: The morphology of miR-196a I/DEAC-PNAG-FA was uniform, and its particle size was approximately 70–100 nm. A nanocarrier with an N/P ratio of 200:1 can maximize the nucleic acid carrying capacity of the self-assembly system. The nanosystem can protect miRNA from RNase degradation and could be internalized rapidly within 4 h. The self-assembly system significantly enhanced the apoptosis-inducing effect of miR-196a I on HepG2 cells (P = 0.003). Molecular biological analyses confirmed that the apoptosis-inducing effect of the nanosystem was due to the inhibition of miR-196a gene expression in HepG2 cells, which upregulate the expression of pro-apoptotic proteins FOXO1 (P < 0.001), Bax (P < 0.001), Ki67 (P < 0.001), and proliferating cell nuclear antigen (P < 0.001), and inhibit the expression of apoptosis inhibitory protein Bcl-2 (P < 0.001). Moreover, compared with free miR-196a inhibitor or miR-196a I/DEAC-PNAG, miR-196a I/DEAC-PNAG-FA can more effectively inhibit tumor growth in vivo (P = 0.026). Conclusion: The newly prepared self-assembly targeting system can effectively induce apoptosis and abrogate tumor growth, which may open a new approach for liver cancer treatment.https://balkanmedicaljournal.org/text.php?lang=en&id=2364 |
| spellingShingle | Yuxia Hao Xi Li Deacetylated-poly-N-acetylglucosamine-folic Acid as a Nanocarrier for Delivering miR-196a Inhibitor to Anticancer Activity Balkan Medical Journal |
| title | Deacetylated-poly-N-acetylglucosamine-folic Acid as a Nanocarrier for Delivering miR-196a Inhibitor to Anticancer Activity |
| title_full | Deacetylated-poly-N-acetylglucosamine-folic Acid as a Nanocarrier for Delivering miR-196a Inhibitor to Anticancer Activity |
| title_fullStr | Deacetylated-poly-N-acetylglucosamine-folic Acid as a Nanocarrier for Delivering miR-196a Inhibitor to Anticancer Activity |
| title_full_unstemmed | Deacetylated-poly-N-acetylglucosamine-folic Acid as a Nanocarrier for Delivering miR-196a Inhibitor to Anticancer Activity |
| title_short | Deacetylated-poly-N-acetylglucosamine-folic Acid as a Nanocarrier for Delivering miR-196a Inhibitor to Anticancer Activity |
| title_sort | deacetylated poly n acetylglucosamine folic acid as a nanocarrier for delivering mir 196a inhibitor to anticancer activity |
| url | https://balkanmedicaljournal.org/text.php?lang=en&id=2364 |
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