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Evaluation of the potential of a simplified co-delivery system with oligodeoxynucleotides as a drug carrier for enhanced antitumor effect

Authors Liu CX, Liu TX, Liu YJ, Zhang N

Received 25 October 2017

Accepted for publication 17 February 2018

Published 20 April 2018 Volume 2018:13 Pages 2435—2445

DOI https://doi.org/10.2147/IJN.S155135

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Govarthanan Muthusamy

Peer reviewer comments 5

Editor who approved publication: Dr Linlin Sun


Chunxi Liu,1,* Tingxian Liu,2,* Yongjun Liu,2 Na Zhang2

1Department of Pharmacy, Qilu Hospital, Shandong University, Ji’nan, China; 2School of Pharmaceutical Science, Shandong University, Ji’nan, China

*These authors contributed equally to this work

Background: We previously developed a simple effective system based on oligodeoxynucleotides with CGA repeating units (CGA-ODNs) for Dox and siRNA intracellular co-delivery.
Methods: In the present study, the in vitro cytotoxicity, gene transfection and in vivo safety of the co-delivery system were further characterized and discussed.
Results:
Compared with poly(ethyleneimine) (PEI), both CGA-ODNs and the pH-sensitive targeted coating, o-carboxymethyl-chitosan (CMCS)-poly(ethylene glycol) (PEG)-aspargine-glycine-arginine (NGR) (CMCS-PEG-NGR, CPN) showed no obvious cytotoxicity in 72 h. The excellent transfection capability of CPN coated Dox and siRNA co-loaded nanoparticles (CPN-PDR) was confirmed by real-time PCR and Western blot analysis. It was calculated that there was no significant difference in silencing efficiency among Lipo/siRNA, CPN-modified siRNA-loaded nanoparticles (CPN-PR) and CPN-PDR. Furthermore, CPN-PDR was observed to be significantly much more toxic than Dox- and CPN-modified Dox-loaded nanoparticles (CPN-PD), implying their higher antitumor potential. Both hemolysis tests and histological assessment implied that CPN-PDR was safe for intravenous injection with nontoxicity and good biocompatibility in vitro and in vivo.
Conclusion:
The results indicated that CPN-PDR could be a potentially promising co-delivery carrier for enhanced antitumor therapy.

Keywords: co-delivery, doxorubicin, VEGF, cytotoxicity, transfection

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