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

• Published in: Advanced healthcare materials Vol. 12; no. 3; pp. e2201306 - n/a
• Main Authors: Li, Meirong, Lin, Zheng‐Ian, Yang, Jingyu, Huang, Haoqiang, Liu, Guan‐Lin, Liu, Qiqi, Zhang, Xinmeng, Zhang, Ying, Xu, Zhourui, Lin, Haoming, Chai, Yujuan, Chen, Xin, Ko, Bao‐Tsan, Liu, Jia, Chen, Chih‐Kuang, Yang, Chengbin
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.01.2023
• Subjects: Apoptosis; Biodegradability; Bone cancer; Bone Neoplasms; Cancer; Carbon Dioxide; Carbonates; cationic polycarbonates; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Line, Tumor; Cell proliferation; Expression vectors; Gene expression; Gene therapy; Genetic Therapy - methods; Genetic Vectors; Humans; In vivo methods and tests; Invasiveness; Kinases; Nanoparticles; Nanotechnology; Osteosarcoma; Osteosarcoma cells; PLK1; Polo-like kinase 1; RNA, Small Interfering - genetics; RNA-mediated interference; Sarcoma; siRNA; siRNA delivery; Therapeutic targets; Transfection; Tumors; siRNA delivery; gene therapy; osteosarcoma; PLK1; cationic polycarbonates
• ISSN: 2192-2640; 2192-2659; 2192-2659
• DOI: 10.1002/adhm.202201306

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 G2/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. Exhibiting limited cytotoxicity and prominent transfection efficiency, biodegradable and CO2‐derivative cationic poly(vinylcyclohexene carbonates) (CPCHCs) are used as gene vectors for osteosarcoma treatment. CPCHC/siPLK1 nanoparticles can inhibit expression of PLK1 at the transcriptional and translational levels, leading to cell arrest in G2/M phase and cell death from apoptosis, and finally, significantly inhibit osteosarcoma in vitro and in vivo.