title: Nucleolin targeting AS1411 modified protein nanoparticle for antitumor drugs delivery.
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.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Wu
authors.forename: Chenchen
authors.initials: C
authors.lastname: Song
authors.forename: Chenxiao
authors.initials: C
authors.lastname: Jiang
authors.forename: Xin
authors.initials: X
authors.lastname: Shen
authors.forename: Qian
authors.initials: Q
authors.lastname: Qiao
authors.forename: Yiqiao
authors.initials: Y
authors.lastname: Hu
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D043169:Endostatins / Q000494:pharmacology; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000378:metabolism / Q000494:pharmacology; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000097796:Nucleolin
chemical_list: D000970:Antineoplastic Agents; D043169:Endostatins; D017239:Paclitaxel; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D000097796:Nucleolin