Journal
MOLECULAR PHARMACEUTICS
Volume 10, Issue 10, Pages 3555-3563Publisher
AMER CHEMICAL SOC
DOI: 10.1021/mp300686g
Keywords
aptamer AS1411; nucleolin targeting; nanoparticle; paclitaxel; antitumor therapy
Funding
- Research Fund for the Doctoral Program of Higher Education of China [20110091120044]
- Natural Science Foundation of Jiangsu [BK2011572, BK2011859, BK2011539]
- National Natural Science Foundation [81202474, 3097365, 811722661]
- Changzhou Special Project of Biotechnology and Biopharmacy [CE20105006]
- Science & Technology Support Program of Jiangsu Province [BE2010719]
- Post-doctoral Foundation [2012M521051]
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Over recent years, cell surface nucleolin as an anticancer target has attracted many researchers' attentions. To improve the antitumor efficacy, we developed a nucleolin targeted protein nanoparticle (NTPN) delivery system in which human serum albumin (HSA) was used as drug carrier and a DNA aptamer named AS 1411, which had high affinity to nucleolin, was used as a bullet. The HSA nanoparticles (NPs-PTX) were fabricated by a novel self-assembly method and then modified with AS1411 (Apt-NPs-PTX). The resulted Apt-NPs-PTX were spherical. Compared with NPs-PTX, the uptake of Apt-NPs-PTX displayed a significant increase in MCF-7 cells while there was a decrease in nontumor cell lines such as MCF-10A and 3T3 cells. In a cytotoxic study, Apt-NPs-PTX displayed an enhanced cytotoxicity in MCF-7 tumor cells while there was almost no cytotcoxicity in MCF-10A cells. Endostatin, a nucleolin inhibitor, could significantly decrease the internalization of Apt-NPs-PTX, suggesting nucleolin mediates the transmembrane process of Apt-NPs-PTX. Therefore, the AS 1411 modified NTPN delivery system might be a promising targeted drug delivery system.
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