Codelivery of temozolomide and siRNA with polymeric nanocarrier for effective glioma treatment
Received 4 February 2018
Accepted for publication 26 April 2018
Published 15 June 2018 Volume 2018:13 Pages 3467—3480
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Alexander Kharlamov
Peer reviewer comments 2
Editor who approved publication: Dr Lei Yang
Yuan Peng,1,2 Jinsheng Huang,2 Hong Xiao,2 Teng Wu,1 Xintao Shuai1,2
1Center of Biomedical Engineering, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China; 2Key Laboratory for Polymeric Composite & Functional Materials of Ministry of Education, Department of Polymer Science, School of Materials Science and Engineering, Sun Yat-Sen University, Guangzhou 510275, China
Background: The treatment of glioma remains a challenge because conventional chemotherapy is often ineffective by drug resistance. Combinative therapy using chemotherapeutic agents and siRNA has demonstrated potential to improve anticancer outcome through a synergistic effect in various cancers. The current study aims to achieve better glioma treatment through a combinative therapy based on a folate-targeted nanocarrier carrying both temozolomide (TMZ) and anti-BCL-2 siRNA.
Methods: A polymeric micelle (TMZ-FaPEC@siRNA) incorporating TMZ and anti-BCL-2 siRNA was prepared based on folate-conjugated triblock copolymer (Fa-PEG-PEI-PCL, Fa-PEC) of poly(ε-caprolactone) (PCL), poly(ethylenimine) (PEI) and poly(ethylene glycol) (PEG). The physicochemical properties and drug release profile of TMZ-FaPEC@siRNA were tested. The Fa-targeted drug delivery and joint effect of siRNA and TMZ to induce glioma apoptosis and tumor growth inhibition were evaluated both in vitro and in vivo.
Results: In vitro cell study demonstrated that the nanocarrier effectively facilitates codelivery of siRNA and TMZ into C6 cells, resulting in a strong apoptotic response of cancer cells by silencing the antiapoptosis BCL-2 gene and activating the proapoptotic Bax gene simultaneously. In vivo study in rat bearing orthotropic glioma showed that tumor growth was inhibited and meanwhile animal survival was prolonged remarkably through intracranial injection of TMZ-FaPEC@siRNA.
Conclusion: Our results evidence the strong efficacy of the folate-targeted nanomedicine carrying TMZ and BCL-2 siRNA in treating glioma.
Keywords: polymeric nanocarrier, temozolomide, siRNA targeting BCL-2 gene, glioma treatment, drug resistance
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