The Promising Nanocarrier for Doxorubicin and siRNA Co-delivery by PDMAEMA-based Amphiphilic Nanomicelles
2016
Cheng, Qiang | Du, Lili | Meng, Lingwei | Han, Shangcong | Wei, Tuo | Wang, Xiaoxia | Wu, Yidi | Song, Xinyun | Zhou, Junhui | Zheng, Shuquan | Huang, Yuanyu | Liang, Xing-Jie | Cao, Huiqing | Dong, Anjie | Liang, Zicai
Synergistic effects of anticancer drug and siRNA have displayed superior advantages for cancer therapy. Herein, we deeply analyzed the feasibility that whether doxorubicin (DOX) and siRNA could be co-delivered by mPEG–PCL-graft-PDMAEMA (PECD) micelles, which mediated excellent DNA/siRNA delivery in vitro and in vivo reported in our previous work. DOX-loaded NPs (PECD-D) were developed by nanoprecipitation technology and exhibited high drug loading content (DLC, 9.5%). In vitro cytotoxicity study in MDA-MB-231 cells, PECD-D treated groups had lower IC₅₀ compared to free DOX groups (F-DOX) at different transfection time (24, 48, and 72h), which maybe attribute to its high cellular uptake and endosomal escape properties. The speculation was confirmed with the results of drug release profile in acidic media, flow cytometry analysis and confocal images. Futhermore, Cy5 labeled siRNA was introduced in PECD-D micelles (PECD-D/siRNA) to track the behavior of dual-loaded nanodrug in vitro and in vivo. Flow cytometry analysis presented that DOX and siRNA were successfully co-delivered into cells, the positive cells ratio were 94.6 and 99.5%, respectively. Confocal images showed that not only DOX and siRNA existed in cytoplasm, but DOX traversed endosome/lysosome and entered into cell nucleus. For in vivo tumor-targeting evaluation in BALB/c nude mice, both DOX and Cy5-siRNA could be detected in tumor sites after intravenous injection with PECD-D/siRNA formulation. Therefore, we believed that PECD micelles have a potential ability as DOX and siRNA co-delivery carrier for cancer therapy.
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