顺铂
卵巢癌
奥拉帕尼
癌症研究
药理学
化学
药物输送
体内
化疗
医学
生物
聚ADP核糖聚合酶
生物化学
聚合酶
癌症
内科学
基因
生物技术
有机化学
作者
Mengdi Song,Fang Zhou,Jun Wang,Kehai Liu
标识
DOI:10.1016/j.ijpharm.2023.123022
摘要
Ovarian cancer (OC) has a low five-year survival rate, mainly because of its drug resistance to chemotherapy. It is the key to reverse drug resistance to combine multiple sensitization pathways to play a synergistic role. A nano scaled targeted co-delivery system (P123-PEI-G12, PPG) modified by bifunctional peptide tLyP-1-NLS (G12) was fabricated by using Pluronic P123 conjugated with low molecular weight polyethyleneimine (PEI). This delivery system can co-delivery Olaparib (Ola) and p53 plasmids to synergistically enhance the sensitivity of OC to platinum-based chemotherapy. P53@P123-PEI-G2/Ola (Co-PPGs) can achieve efficient tumor accumulation and cellular internalization through G12-mediated targeting. Co-PPGs then break down in the tumor cells, releasing the drug. Co-PPGs significantly enhanced the sensitivity of cisplatin (DDP) in platinum-resistant ovarian cancer (PROC) and synergistically inhibited the proliferation of PROC in vitro and in vivo. The sensitizing and synergistic effects of Co-PPGs were related to the activation of p53, inhibition of poly-ADP-ribose polymerase (PARP) and p-glycoprotein (P-gp) expression. This work provides a promising strategy for the effective treatment of PROC.
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