Nucleolin Targeting AS1411 Modified Protein Nanoparticle for Antitumor Drugs Delivery

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Abstract

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 AS1411, 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 cytotoxicity 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 AS1411 modified NTPN delivery system might be a promising targeted drug delivery system.

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