Nanoparticles Based on Poly (β-Amino Ester) and HPV16-Targeting CRISPR/shRNA as Potential Drugs for HPV16-Related Cervical Malignancy
Nanoparticles Based on Poly (β-Amino Ester) and HPV16-Targeting CRISPR/shRNA as Potential Drugs for HPV16-Related Cervical Malignancy
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基于聚（β-氨基酯）和 HPV16 靶向 CRISPR/shRNA 的纳米颗粒作为治疗 HPV16 相关宫颈恶性肿瘤的潜在药物。
DOI：
10.1016/j.ymthe.2018.07.019
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发表时间：
2018-10-03
影响因子：
12.4
通讯作者：
Wang, Hui
中科院分区：
文献类型：
--
作者：
Zhu, Da;Shen, Hui;Wang, Hui
持续的高危HPV感染是子宫颈癌的主要原因。HPV致癌基因E7在HPV癌变中起重要作用。目前，人乳头瘤病毒疫苗不能为已经患有宫颈疾病的妇女提供有效的治疗，并且在缺乏医疗资源的国家和地区很难执行推荐的定期宫颈筛查。我们的目标是开发基于聚-氨基酯（PBAE）和HPV16 E7靶向CRISPR/短发卡RNA （shRNA）的纳米颗粒（NPs），以降低HPV16 E7的水平，作为治疗HPV感染及其相关宫颈恶性肿瘤的初步药物形式。我们的NPs在细胞和小鼠器官中显示出低毒性。通过降低HPV16 E7的表达，我们的NPs可以抑制裸鼠宫颈癌细胞和异种移植瘤的生长，并可以逆转HPV16转基因小鼠的恶性宫颈上皮表型。含有shRNA的NPs的性能优于含有CRISPR的NPs。由PBAE和CRISPR/shRNA组成的HPV靶向NPs可能被开发为治疗HPV感染和HPV相关宫颈恶性肿瘤的药物。
Persistent high-risk HPV infection is the main cause of cervical cancer. The HPV oncogene E7 plays an important role in HPV carcinogenesis. Currently, HPV vaccines do not offer an effective treatment for women who already present with cervical disease, and recommended periodical cervical screenings are difficult to perform in countries and areas lacking medical resources. Our aim was to develop nanoparticles (NPs) based on poly (beta-amino ester) (PBAE) and HPV16 E7-targeting CRISPR/short hairpin RNA (shRNA) to reduce the levels of HPV16 E7 as a preliminary form of a drug to treat HPV infection and its related cervical malignancy. Our NPs showed low toxicity in cells and mouse organs. By reducing the expression of HPV16 E7, our NPs could inhibit the growth of cervical cancer cells and xenograft tumors in nude mice, and they could reverse the malignant cervical epithelium phenotype in HPV16 transgenic mice. The performance of NPs containing shRNA is better than that of NPs containing CRISPR. HPV-targeting NPs consisting of PBAE and CRISPR/shRNA could potentially be developed as drugs to treat HPV infection and HPV-related cervical malignancy.