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

被引:8
作者
Li, Meirong [1 ,2 ]
Lin, Zheng-Ian [3 ]
Yang, Jingyu [2 ]
Huang, Haoqiang [2 ]
Liu, Guan-Lin [4 ]
Liu, Qiqi [2 ]
Zhang, Xinmeng [2 ]
Zhang, Ying [1 ,2 ]
Xu, Zhourui [2 ]
Lin, Haoming [2 ]
Chai, Yujuan [2 ]
Chen, Xin [2 ]
Ko, Bao-Tsan [4 ]
Liu, Jia [1 ]
Chen, Chih-Kuang [3 ]
Yang, Chengbin [2 ]
机构
[1] Chinese Univ Hong Kong, Affiliated Hosp 2, Shenzhen & Longgang Dist Peoples Hosp Shenzhen, Sch Med,Cent Lab, Shenzhen 518172, Guangdong, Peoples R China
[2] Shenzhen Univ, Hlth Sci Ctr, Sch Biomed Engn, Guangdong Key Lab Biomed Measurements & Ultrasoun, Shenzhen 518060, Peoples R China
[3] Natl Sun Yat Sen Univ, Dept Mat & Optoelect Sci, Polymer Biomat Lab, Kaohsiung 80424, Taiwan
[4] Natl Chung Hsing Univ, Dept Chem, Taichung 40227, Taiwan
基金
中国国家自然科学基金;
关键词
cationic polycarbonates; gene therapy; osteosarcoma; PLK1; siRNA delivery; KINASE; 1; SIRNA DELIVERY; POLYCARBONATES; NANOPARTICLES; DRUG; POLYLACTIDE; TARGETS; SIPLK1;
D O I
10.1002/adhm.202201306
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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.
引用
收藏
页数:15
相关论文
共 72 条
[1]   Polymer gene delivery: overcoming the obstacles [J].
Aied, Ahmed ;
Greiser, Udo ;
Pandit, Abhay ;
Wang, Wenxin .
DRUG DISCOVERY TODAY, 2013, 18 (21-22) :1090-1098
[2]   Review on mechanistic strategy of gene therapy in the treatment of disease [J].
Alnasser, Sulaiman M. .
GENE, 2021, 769
[3]   In Vivo Degradation Mechanisms of Aliphatic Polycarbonates and Functionalized Aliphatic Polycarbonates [J].
Amsden, Brian .
MACROMOLECULAR BIOSCIENCE, 2021, 21 (07)
[4]   Comparison of cationic liposome and PAMAM dendrimer for delivery of anti-Plk1 siRNA in breast cancer treatment [J].
Bulbake, Upendra ;
Kommineni, Nagavendra ;
Ionov, Maksim ;
Bryszewska, Maria ;
Khan, Wahid .
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY, 2020, 25 (01) :9-19
[5]   Facile Synthesis of a Carnosine-Pendent Cationic Polymer via Free Radical Polymerization and Application in Gene Delivery [J].
Cao, Leilei ;
Li, Xiao ;
Wu, Tiantian ;
Cai, Xuetong ;
Zhang, Yajie ;
Ji, Jinkai ;
Zhang, Xiaoran ;
Gao, Yajing ;
Feng, Fude .
MACROMOLECULAR CHEMISTRY AND PHYSICS, 2019, 220 (15)
[6]  
Cardiff Oncology Inv, 2021, CARDIFF ONCOLOGY ANN
[7]   Biodegradable Polymers for Gene-Delivery Applications [J].
Chen, Chih-Kuang ;
Huang, Ping-Kuan ;
Law, Wing-Cheung ;
Chu, Chia-Hui ;
Chen, Nai-Tzu ;
Lo, Leu-Wei .
INTERNATIONAL JOURNAL OF NANOMEDICINE, 2020, 15 :2131-2150
[8]   Synthesis of Polylactide-Based Core-Shell Interface Cross-Linked Micelles for Anticancer Drug Delivery [J].
Chen, Chih-Kuang ;
Lin, Wei-Jen ;
Hsia, Yu ;
Lo, Leu-Wei .
MACROMOLECULAR BIOSCIENCE, 2017, 17 (03)
[9]   Poly(ethylene glycol)-block-cationic polylactide nanocomplexes of differing charge density for gene delivery [J].
Chen, Chih-Kuang ;
Jones, Charles H. ;
Mistriotis, Panagiotis ;
Yu, Yun ;
Ma, Xiaoni ;
Ravikrishnan, Anitha ;
Jiang, Ming ;
Andreadis, Stelios T. ;
Pfeifer, Blaine A. ;
Cheng, Chong .
BIOMATERIALS, 2013, 34 (37) :9688-9699
[10]   Well-Defined Degradable Cationic Polylactide as Nanocarrier for the Delivery of siRNA to Silence Angiogenesis in Prostate Cancer [J].
Chen, Chih-Kuang ;
Law, Wing-Cheung ;
Aalinkeel, Ravikumar ;
Nair, Bindukumar ;
Kopwitthaya, Atcha ;
Mahajan, Supriya D. ;
Reynolds, Jessica L. ;
Zou, Jiong ;
Schwartz, Stanley A. ;
Prasad, Paras N. ;
Cheng, Chong .
ADVANCED HEALTHCARE MATERIALS, 2012, 1 (06) :751-761