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Combined Delivery of Temozolomide and siPLK1 Using Targeted Nanoparticles to Enhance Temozolomide Sensitivity in Glioma

Authors Shi H, Sun S, Xu H, Zhao Z, Han Z, Jia J, Wu D, Lu J, Liu H, Yu R

Received 27 December 2019

Accepted for publication 15 April 2020

Published 12 May 2020 Volume 2020:15 Pages 3347—3362

DOI https://doi.org/10.2147/IJN.S243878

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Mian Wang


Hui Shi,1,2,* Shuo Sun,1,* Haoyue Xu,3,* Zongren Zhao,3 Zhengzhong Han,3 Jun Jia,3 Dongmei Wu,4 Jun Lu,4 Hongmei Liu,3,5 Rutong Yu1,3,5

1Clinical Medical College, Nanjing Medical University, Nanjing, People’s Republic of China; 2The Second People’s Hospital of Lianyungang, Lianyungang, People’s Republic of China; 3Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, People’s Republic of China; 4Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, People’s Republic of China; 5Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Rutong Yu; Hongmei Liu Tel +86 13182310079
; +86 17716228111
Email yu.rutong@163.com; liuhongmei816@sina.com

Introduction: Temozolomide (TMZ) is the first-line chemotherapeutic option to treat glioma; however, its efficacy and clinical application are limited by its drug resistance properties. Polo-like kinase 1 (PLK1)-targeted therapy causes G2/M arrest and increases the sensitivity of glioma to TMZ. Therefore, to limit TMZ resistance in glioma, an angiopep-2 (A2)-modified polymeric micelle (A2PEC) embedded with TMZ and a small interfering RNA (siRNA) targeting PLK1 (siPLK1) was developed (TMZ-A2PEC/siPLK).
Materials and Methods: TMZ was encapsulated by A2-PEG-PEI-PCL (A2PEC) through the hydrophobic interaction, and siPLK1 was complexed with the TMZ-A2PEC through electrostatic interaction. Then, an angiopep-2 (A2) modified polymeric micelle (A2PEC) embedding TMZ and siRNA targeting polo-like kinase 1 (siPLK1) was developed (TMZ-A2PEC/siPLK).
Results: In vitro experiments indicated that TMZ-A2PEC/siPLK effectively enhanced the cellular uptake of TMZ and siPLK1 and resulted in significant cell apoptosis and cytotoxicity of glioma cells. In vivo experiments showed that glioma growth was inhibited, and the survival time of the animals was prolonged remarkably after TMZ-A2PEC/siPLK1 was injected via their tail vein.
Discussion: The results demonstrate that the combination of TMZ and siPLK1 in A2PEC could enhance the efficacy of TMZ in treating glioma.

Keywords: co-delivery, polymeric micelle, siPLK1, TMZ, drug resistance, glioma

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