AUTHOR=Xiong Jinfeng , Li Guannan , Mei Xinyu , Ding Jiahui , Shen Hui , Zhu Da , Wang Hui 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.826771

DOI=10.3389/fphar.2022.826771

ISSN=1663-9812

ABSTRACT=<p>The <italic>p53</italic> 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. <italic>P53</italic> was inactivated by HPV oncoprotein <italic>E6</italic>, promoting abnormal cell proliferation and carcinogenesis. To study the treatment of cervical intraepithelial neoplasia (CIN) and cervical cancer by restoring <italic>p53</italic> 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 <italic>p53</italic> and targeting <italic>E7</italic>). <italic>In vitro</italic> and <italic>in vivo</italic> 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 <italic>p53</italic> expression and the inactivation of HPV16 <italic>E7</italic> are essential for blocking the development of cervical cancer. This study provides new insights into the precise treatment of HPV-related cervical lesions.</p>