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. 2012 Jul;33(20):5115-23.
doi: 10.1016/j.biomaterials.2012.03.058. Epub 2012 Apr 6.

Precise glioma targeting of and penetration by aptamer and peptide dual-functioned nanoparticles

Huile Gao  1 , Jun Qian, Shijie Cao, Zhi Yang, Zhiqing Pang, Shuaiqi Pan, Li Fan, Zhangjie Xi, Xinguo Jiang, Qizhi Zhang
Affiliations

Precise glioma targeting of and penetration by aptamer and peptide dual-functioned nanoparticles

Huile Gao et al. Biomaterials. 2012 Jul.

Abstract

The treatment of a brain glioma is still one of the most difficult challenges in oncology. To effectively treat brain glioma and reduce the side effects, drugs must be transported across the blood brain barrier (BBB) and then targeted to the brain cancer cells because most anti-tumor drugs are highly toxic to the normal brain tissue. A cascade delivery strategy was developed to perform these two aims and to achieve enhanced and precisely targeted delivery. Herein, we utilize a phage-displayed TGN peptide and an AS1411 aptamer, which are specific targeting ligands of the BBB and cancer cells, respectively and we conjugate them with nanoparticles to establish the brain glioma cascade delivery system (AsTNP). In vitro cell uptake and three-dimensional tumor spheroid penetration studies demonstrated that the system could not only target endothelial and tumor cells but also penetrate the endothelial monolayers and tumor cells to reach the core of the tumor spheroids, which was extremely important but mostly ignored in glioma therapy. In vivo imaging further demonstrated that the AsTNP provided the highest tumor distribution and tumor/normal brain ratio. The distribution was also reconfirmed by fluorescent images of the brain slides. As a result, the docetaxel-loaded AsTNP presents the best anti-glioma effect with improved glioma bearing survival. In conclusion, the AsTNP could precisely target to the brain glioma, which was a valuable target for glioma imaging and therapy.

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