4.7 Article

Biodegradable Carbon Dioxide-Derived Non-Viral Gene Vectors for Osteosarcoma Gene Therapy

期刊

ADVANCED HEALTHCARE MATERIALS
卷 12, 期 3, 页码 -

出版社

WILEY
DOI: 10.1002/adhm.202201306

关键词

cationic polycarbonates; gene therapy; osteosarcoma; PLK1; siRNA delivery

向作者/读者索取更多资源

Osteosarcoma is a highly invasive and deadly cancer that often occurs in children and adolescents. The overexpression of PLK1 gene in tumors promotes cancer cell proliferation and transformation, making it a therapeutic target for osteosarcoma. However, current RNA interference-based therapies lack a safe and efficient nonviral gene vector. In this study, biodegradable and CO2-derivative cationic poly(vinylcyclohexene carbonates) (CPCHCs) were used as gene vectors for siPLK1 therapeutic strategy in osteosarcoma treatment. Among them, CPCHC60 showed excellent performance in gene transfection efficiency, endo-lysosome escaping, biodegradability, and biosafety. The treatment with CPCHCs/siRNA nanoparticles significantly down-regulated the expression level of PLK1 gene in osteosarcoma cells, leading to cell arrest and apoptosis, resulting in significant tumor regression both in vitro and in vivo. This study provides new insights into the development of superior nonviral gene vectors for cancer treatment and holds high potential for translational nanomedicine applications.
Osteosarcoma often occurs in children and adolescents with high invasiveness and high mortality. Polo-like kinase 1 (PLK1) overexpressed in most tumors promotes cancer cell proliferation and transformation. PLK1 is considered as a therapeutic target for osteosarcoma. RNA interference-based therapies are employed to combat osteosarcoma through silencing PLK1 gene expression. However, the treatment results remain unsatisfactory due to the lack of a safe and efficient nonviral gene vector. To tackle this hurdle, biodegradable and CO2-derivative cationic poly(vinylcyclohexene carbonates) (CPCHCs) are used as gene vectors to perform a siPLK1 therapeutic strategy for osteosarcoma treatment. Of those CPCHCs, CPCHC60 demonstrates the most excellent performance in gene transfection efficiency, endo-lysosome escaping, biodegradability, and biosafety. With the treatment of CPCHCs/siRNA nanoparticles, the expression level of PLK1 gene in osteosarcoma cells is significantly down-regulated. Subsequently, cells are arrested in the G(2)/M phase and subsequently dead in the form of apoptosis, resulting in significant tumor regression both in vitro and in vivo. This study brings a new insight into the development of superior nonviral gene vectors for practical cancer treatment. Based on the results, the resulting nanoparticle-based gene drug formation is considered to have a highly successful chance in further translational nanomedicine applications.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据