Aurora kinase B siRNA-loaded lactoferrin nanoparticles potentiate the efficacy of temozolomide in treating glioblastoma

被引:25
|
作者
Kumari, Sonali [1 ]
Bhattacharya, Dwaipayan [2 ]
Rangaraj, Nandini [3 ]
Chakarvarty, Sumana [3 ]
Kondapi, Anand K. [1 ]
Rao, Nalam M. [2 ]
机构
[1] Univ Hyderabad, Sch Life Sci, Dept Biotechnol & Bioinformat, Prof CR Rao Rd, Hyderabad 500046, Telangana, India
[2] CSIR, Indian Inst Chem Technol, Ctr Chem Biol, Hyderabad 500007, Telangana, India
[3] CSIR, CCMB, Uppal Rd, Hyderabad 500007, Telangana, India
关键词
blood-brain barrier; glioblastoma multiforme; nanoparticle; siRNA; temozolomide; MEDIATED TARGETED DELIVERY; CANCER STEM-CELLS; LIPID NANOPARTICLES; SYSTEMIC DELIVERY; MOUSE MODEL; GENE; DNA; DRUG; PHARMACOKINETICS; PHOSPHORYLATION;
D O I
10.2217/nnm-2018-0110
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Aim: To investigate the efficacy of lactoferrin nanoparticles (LfNPs) in delivering siRNA across the bloodbrain barrier to treat glioblastoma multiforme (GBM) and with an additional objective of potentiation of conventional temozolomide (TMZ) chemotherapy. Methods: Aurora kinase B (AKB) siRNA-loaded nanoparticles (AKB-LfNPs) were prepared with milk protein, lactoferrin, by water in oil emulsion method. AKB-LfNPs were tested in cell lines and in GBM orthotopic mouse model with and without TMZ treatment. Results: AKB silencing, cytotoxicity and cell cycle arrest by these LfNPs were shown to be effective on GL261 cells. Tumor growth was significantly lower in AKB-LfNPs alone and in combination with TMZ treated mice and increased the survival by 2.5-times. Conclusion: Treatment of AKB-LfNPs to GBM mice improves life expectancy and has potential to combine with conventional chemotherapy.
引用
收藏
页码:2579 / 2596
页数:18
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