Co-Delivery of p53 Restored and E7 Targeted Nucleic Acids by Poly (Beta-Amino Ester) Complex Nanoparticles for the Treatment of HPV Related Cervical Lesions
The p53 gene has the highest mutation frequency in tumors, and its inactivation can lead to malignant transformation, such as cell cycle arrest and apoptotic inhibition. Persistent high-risk human papillomavirus (HR-HPV) infection is the leading cause of cervical cancer. P53 was inactivated by HPV o...
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| Format: | Article |
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.826771/full |
| _version_ | 1798031858983763968 |
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| author | Jinfeng Xiong Guannan Li Xinyu Mei Jiahui Ding Hui Shen Da Zhu Hui Wang |
| author_facet | Jinfeng Xiong Guannan Li Xinyu Mei Jiahui Ding Hui Shen Da Zhu Hui Wang |
| author_sort | Jinfeng Xiong |
| collection | DOAJ |
| description | The p53 gene has the highest mutation frequency in tumors, and its inactivation can lead to malignant transformation, such as cell cycle arrest and apoptotic inhibition. Persistent high-risk human papillomavirus (HR-HPV) infection is the leading cause of cervical cancer. P53 was inactivated by HPV oncoprotein E6, promoting abnormal cell proliferation and carcinogenesis. To study the treatment of cervical intraepithelial neoplasia (CIN) and cervical cancer by restoring p53 expression and inactivating HPV oncoprotein, and to verify the effectiveness of nano drugs based on nucleic acid delivery in cancer treatment, we developed poly (beta-amino ester)537, to form biocompatible and degradable nanoparticles with plasmids (expressing p53 and targeting E7). In vitro and in vivo experiments show that nanoparticles have low toxicity and high transfection efficiency. Nanoparticles inhibited the growth of xenograft tumors and successfully reversed HPV transgenic mice’s cervical intraepithelial neoplasia. Our work suggests that the restoration of p53 expression and the inactivation of HPV16 E7 are essential for blocking the development of cervical cancer. This study provides new insights into the precise treatment of HPV-related cervical lesions. |
| first_indexed | 2024-04-11T20:03:19Z |
| format | Article |
| id | doaj.art-3251e7adbee54b3ab32d45722fbd4738 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T20:03:19Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-3251e7adbee54b3ab32d45722fbd47382022-12-22T04:05:26ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-02-011310.3389/fphar.2022.826771826771Co-Delivery of p53 Restored and E7 Targeted Nucleic Acids by Poly (Beta-Amino Ester) Complex Nanoparticles for the Treatment of HPV Related Cervical LesionsJinfeng Xiong0Guannan Li1Xinyu Mei2Jiahui Ding3Hui Shen4Da Zhu5Hui Wang6Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaThe p53 gene has the highest mutation frequency in tumors, and its inactivation can lead to malignant transformation, such as cell cycle arrest and apoptotic inhibition. Persistent high-risk human papillomavirus (HR-HPV) infection is the leading cause of cervical cancer. P53 was inactivated by HPV oncoprotein E6, promoting abnormal cell proliferation and carcinogenesis. To study the treatment of cervical intraepithelial neoplasia (CIN) and cervical cancer by restoring p53 expression and inactivating HPV oncoprotein, and to verify the effectiveness of nano drugs based on nucleic acid delivery in cancer treatment, we developed poly (beta-amino ester)537, to form biocompatible and degradable nanoparticles with plasmids (expressing p53 and targeting E7). In vitro and in vivo experiments show that nanoparticles have low toxicity and high transfection efficiency. Nanoparticles inhibited the growth of xenograft tumors and successfully reversed HPV transgenic mice’s cervical intraepithelial neoplasia. Our work suggests that the restoration of p53 expression and the inactivation of HPV16 E7 are essential for blocking the development of cervical cancer. This study provides new insights into the precise treatment of HPV-related cervical lesions.https://www.frontiersin.org/articles/10.3389/fphar.2022.826771/fullp53human papillomaviruscervical cancerpoly (beta-amino ester)nanoparticle |
| spellingShingle | Jinfeng Xiong Guannan Li Xinyu Mei Jiahui Ding Hui Shen Da Zhu Hui Wang Co-Delivery of p53 Restored and E7 Targeted Nucleic Acids by Poly (Beta-Amino Ester) Complex Nanoparticles for the Treatment of HPV Related Cervical Lesions Frontiers in Pharmacology p53 human papillomavirus cervical cancer poly (beta-amino ester) nanoparticle |
| title | Co-Delivery of p53 Restored and E7 Targeted Nucleic Acids by Poly (Beta-Amino Ester) Complex Nanoparticles for the Treatment of HPV Related Cervical Lesions |
| title_full | Co-Delivery of p53 Restored and E7 Targeted Nucleic Acids by Poly (Beta-Amino Ester) Complex Nanoparticles for the Treatment of HPV Related Cervical Lesions |
| title_fullStr | Co-Delivery of p53 Restored and E7 Targeted Nucleic Acids by Poly (Beta-Amino Ester) Complex Nanoparticles for the Treatment of HPV Related Cervical Lesions |
| title_full_unstemmed | Co-Delivery of p53 Restored and E7 Targeted Nucleic Acids by Poly (Beta-Amino Ester) Complex Nanoparticles for the Treatment of HPV Related Cervical Lesions |
| title_short | Co-Delivery of p53 Restored and E7 Targeted Nucleic Acids by Poly (Beta-Amino Ester) Complex Nanoparticles for the Treatment of HPV Related Cervical Lesions |
| title_sort | co delivery of p53 restored and e7 targeted nucleic acids by poly beta amino ester complex nanoparticles for the treatment of hpv related cervical lesions |
| topic | p53 human papillomavirus cervical cancer poly (beta-amino ester) nanoparticle |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.826771/full |
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