Biodegradable polymers as a noncoding miRNA nanocarrier for multiple targeting therapy of human hepatocellular carcinoma
Therapeutic strategy based on the restoration of tumor suppressor-microRNAs (miRNAs) is a promising approach for cancer therapy, but the low delivery efficiency of miRNA remains a huge hurdle due to the lack of safe and efficient nonviral carriers. In this work, with the use of newly developed PEGyl...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2021
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| Online Access: | https://hdl.handle.net/10356/151662 |
| _version_ | 1826109929457451008 |
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| author | Yang, Chengbin Yin, Ming-jie Xu, Gaixia Lin, Wei-Jen Chen, Jiajie Zhang, Yinling Feng, Tao Huang, Peng Chen, Chih-Kuang Yong, Ken-Tye |
| author2 | School of Electrical and Electronic Engineering |
| author_facet | School of Electrical and Electronic Engineering Yang, Chengbin Yin, Ming-jie Xu, Gaixia Lin, Wei-Jen Chen, Jiajie Zhang, Yinling Feng, Tao Huang, Peng Chen, Chih-Kuang Yong, Ken-Tye |
| author_sort | Yang, Chengbin |
| collection | NTU |
| description | Therapeutic strategy based on the restoration of tumor suppressor-microRNAs (miRNAs) is a promising approach for cancer therapy, but the low delivery efficiency of miRNA remains a huge hurdle due to the lack of safe and efficient nonviral carriers. In this work, with the use of newly developed PEGylated biodegradable charged polyester-based vectors (PEG-BCPVs) as the carrier, the miR26a and miR122 codelivering therapeutic strategy (PEG-BCPVs/miR26a/miR122 as the delivery formulation) is successfully developed for efficient treatment of human hepatocellular carcinoma (HCC). In vitro study results show that PEG-BCPVs are capable of effectively facilitating miRNA cellular uptake via a cell endocytosis pathway. Consequently, the restoration of miR26a and miR122 remarkably inhibit the cell growth, migration, invasion, colony formation, and induced apoptosis of HepG2 cells. More importantly, the chemosensitivity of HepG2 to anticancer drug is also considerably enhanced. After treatment with the PEG-BCPV-based miRNA delivery system, the expression of the multiple targeted genes corresponding to miR26a and miR122 in HepG2 cells is greatly downregulated. Accordingly, the newly developed miRNA restoration therapeutic strategy via biodegradable PEG-BCPVs as the carrier should be a promising modality for combating HCC. |
| first_indexed | 2024-10-01T02:26:08Z |
| format | Journal Article |
| id | ntu-10356/151662 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:26:08Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | ntu-10356/1516622021-07-22T08:56:28Z Biodegradable polymers as a noncoding miRNA nanocarrier for multiple targeting therapy of human hepatocellular carcinoma Yang, Chengbin Yin, Ming-jie Xu, Gaixia Lin, Wei-Jen Chen, Jiajie Zhang, Yinling Feng, Tao Huang, Peng Chen, Chih-Kuang Yong, Ken-Tye School of Electrical and Electronic Engineering Engineering::Electrical and electronic engineering Biodegradable Hepatocellular Carcinoma Therapeutic strategy based on the restoration of tumor suppressor-microRNAs (miRNAs) is a promising approach for cancer therapy, but the low delivery efficiency of miRNA remains a huge hurdle due to the lack of safe and efficient nonviral carriers. In this work, with the use of newly developed PEGylated biodegradable charged polyester-based vectors (PEG-BCPVs) as the carrier, the miR26a and miR122 codelivering therapeutic strategy (PEG-BCPVs/miR26a/miR122 as the delivery formulation) is successfully developed for efficient treatment of human hepatocellular carcinoma (HCC). In vitro study results show that PEG-BCPVs are capable of effectively facilitating miRNA cellular uptake via a cell endocytosis pathway. Consequently, the restoration of miR26a and miR122 remarkably inhibit the cell growth, migration, invasion, colony formation, and induced apoptosis of HepG2 cells. More importantly, the chemosensitivity of HepG2 to anticancer drug is also considerably enhanced. After treatment with the PEG-BCPV-based miRNA delivery system, the expression of the multiple targeted genes corresponding to miR26a and miR122 in HepG2 cells is greatly downregulated. Accordingly, the newly developed miRNA restoration therapeutic strategy via biodegradable PEG-BCPVs as the carrier should be a promising modality for combating HCC. Agency for Science, Technology and Research (A*STAR) Nanyang Technological University This work was supported by the NTU–A*STAR Silicon Technologies, Centre of Excellence, under the program Grant No. 11235100003, the NEWRI seed funding (Grant No. NEWRI SF20140901), the research grants (No. MOST 106-2221-E-224-058; MOST 107-2632-E-035-001; MOST 106-2113-M-039-002-MY2; MOST 107-2221-E-224-059-MY2) supported by the Ministry of Science and Technology of Taiwan, and the School of Electrical and Electronic Engineering at NTU, and the grants from the National Natural Science Foundation of China (NSFC) (81400591). The authors appreciate the Precision Instrument Support Center of Feng Chia University in providing the fabrication and measurement facilities. The authors also gratefully acknowledge the support from Instrumental Analysis Center of Shenzhen University. 2021-07-22T08:56:28Z 2021-07-22T08:56:28Z 2019 Journal Article Yang, C., Yin, M., Xu, G., Lin, W., Chen, J., Zhang, Y., Feng, T., Huang, P., Chen, C. & Yong, K. (2019). Biodegradable polymers as a noncoding miRNA nanocarrier for multiple targeting therapy of human hepatocellular carcinoma. Advanced Healthcare Materials, 8(8), 1801318-. https://dx.doi.org/10.1002/adhm.201801318 2192-2640 0000-0001-9672-7412 https://hdl.handle.net/10356/151662 10.1002/adhm.201801318 30829008 2-s2.0-85062351498 8 8 1801318 en 11235100003 NEWRI SF20140901 Advanced Healthcare Materials © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. All rights reserved. |
| spellingShingle | Engineering::Electrical and electronic engineering Biodegradable Hepatocellular Carcinoma Yang, Chengbin Yin, Ming-jie Xu, Gaixia Lin, Wei-Jen Chen, Jiajie Zhang, Yinling Feng, Tao Huang, Peng Chen, Chih-Kuang Yong, Ken-Tye Biodegradable polymers as a noncoding miRNA nanocarrier for multiple targeting therapy of human hepatocellular carcinoma |
| title | Biodegradable polymers as a noncoding miRNA nanocarrier for multiple targeting therapy of human hepatocellular carcinoma |
| title_full | Biodegradable polymers as a noncoding miRNA nanocarrier for multiple targeting therapy of human hepatocellular carcinoma |
| title_fullStr | Biodegradable polymers as a noncoding miRNA nanocarrier for multiple targeting therapy of human hepatocellular carcinoma |
| title_full_unstemmed | Biodegradable polymers as a noncoding miRNA nanocarrier for multiple targeting therapy of human hepatocellular carcinoma |
| title_short | Biodegradable polymers as a noncoding miRNA nanocarrier for multiple targeting therapy of human hepatocellular carcinoma |
| title_sort | biodegradable polymers as a noncoding mirna nanocarrier for multiple targeting therapy of human hepatocellular carcinoma |
| topic | Engineering::Electrical and electronic engineering Biodegradable Hepatocellular Carcinoma |
| url | https://hdl.handle.net/10356/151662 |
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