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2017, Volume 11, Issue 4

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Frontiers of Chemical Science and Engineering >> 2017, Volume 11, Issue 4 doi: 10.1007/s11705-017-1645-z

Aptamer-coded DNA nanoparticles for targeted doxorubicin delivery using pH-sensitive spacer

. State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostic), Tianjin Medical University, Tianjin 300072, China.. Department of Pharmacy, Ewha Womans University, Seoul 120-750, Korea.. Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, MI 48109-1065, USA

Accepted: 2017-05-10 Available online: 2017-11-06
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Abstract

An anticancer drug delivery system consisting of DNA nanoparticles synthesized by rolling circle amplification (RCA) was developed for prostate cancer membrane antigen (PSMA) targeted cancer therapy. The template of RCA was a DNA oligodeoxynucleotide coded with PSMA-targeted aptamer, drug-loading domain, primer binding site and pH-sensitive spacer. Anticancer drug doxorubicin, as the model drug, was loaded into the drug-loading domain (multiple GC-pair sequences) of the DNA nanoparticles by intercalation. Due to the integrated pH-sensitive spacers in the nanoparticles, in an acidic environment, the cumulative release of doxorubicin was far more than the cumulative release of the drug in the normal physiological environment. In cell uptake experiments, treated with doxorubicin loaded DNA nanoparticles, PSMA-positive C4-2 cells could take up more doxorubicin than PSMA-null PC-3 cells. The prepared DNA nanoparticles showed the potential as drug delivery system for PSMA targeting prostate cancer therapy.

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