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.
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.
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DOI：
10.3389/fphar.2022.826771
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发表时间：
2022
影响因子：
5.6
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Xiong J;Li G;Mei X;Ding J;Shen H;Zhu D;Wang H
p53基因在肿瘤中突变频率最高，其失活可导致恶性转化，如细胞周期停滞和凋亡抑制。宫颈癌的病因有哪些？宫颈癌的病因有哪些？HPV癌蛋白E6使P53失活，促进细胞异常增殖和癌变。为了研究通过恢复p53表达和灭活HPV癌蛋白来治疗宫颈上皮内瘤变（CIN）和宫颈癌，并验证基于核酸递送的纳米药物在癌症治疗中的有效性，我们开发了聚（β-氨基酯）537，以与质粒（表达p53并靶向E7）形成生物相容性和可降解的纳米颗粒。体内外实验表明，纳米粒具有低毒性和高转染效率。纳米颗粒抑制了异种移植肿瘤的生长，并成功逆转了HPV转基因小鼠的宫颈上皮内瘤变。我们的工作表明，p53表达的恢复和HPV 16 E7的失活对于阻断宫颈癌的发展是必不可少的。这项研究为HPV相关宫颈病变的精确治疗提供了新的见解。
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.
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影响因子：
17.1
作者：
Guerrero-Cazares, Hugo;Tzeng, Stephany Y.;Young, Noah P.;Abutaleb, Ameer O.;Quinones-Hinojosa, Alfredo;Green, Jordan J.
通讯作者：
Green, Jordan J.
影响因子：
5.6
作者：
Granados-López AJ;Manzanares-Acuña E;López-Hernández Y;Castañeda-Delgado JE;Fraire-Soto I;Reyes-Estrada CA;Gutiérrez-Hernández R;López JA
通讯作者：
López JA
影响因子：
28.5
作者：
Hu J;Cao J;Topatana W;Juengpanich S;Li S;Zhang B;Shen J;Cai L;Cai X;Chen M
通讯作者：
Chen M
DOI：
10.1038/s41568-020-00315-z
发表时间：
2021-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Klco JM;Mullighan CG
通讯作者：
Mullighan CG
影响因子：
46.9
作者：
Evers, Bastiaan;Jastrzebski, Katarzyna;Bernards, Rene
通讯作者：
Bernards, Rene