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Induction of Au-methotrexate conjugates by sugar molecules: production, assembly mechanism, and bioassay studies

Wang, WY (Wang, Wei-Yuan)[ 1 ] ; Zhao, XF (Zhao, Xiu-Fen)[ 1 ] ; Ju, XH (Ju, Xiao-Han)[ 1 ] ; Liu, P (Liu, Ping)[ 1 ] ; Li, J (Li, Jing)[ 1 ] ; Tang, YW (Tang, Ya-Wen)[ 1 ] ; Li, SP (Li, Shu-Ping)[ 1,2 ]*（李淑萍）; Li, XD (Li, Xiao-Dong)[ 1 ]*（李曉東）; Song, FG (Song, Fu-Gui)[ 2 ]

[ 1 ] Nanjing Normal Univ, Sch Chem & Mat Sci, Jiangsu Key Lab Biofunct Mat, Nanjing 210023, Jiangsu, Peoples R China

[ 2 ] Shandong Bingkun Tengtai Ceram Technol Co Ltd, Zibo 255321, Peoples R China

INTERNATIONAL JOURNAL OF PHARMACEUTICS，201803,538(1-2), 65-78

Au-methotrexate (Au-MTX) conjugates induced by sugar molecules were produced by a simple, one-pot, hydrothermal growth method. Herein, the Au(III)-MTX complexes were used as the precursors to form Au-MTX conjugates. Addition of different types of sugar molecules with abundant hydroxyl groups resulted in the formation of Au-MTX conjugates featuring distinct characteristics that could be explained by the diverse capping mechanisms of sugar molecules. That is, the instant-capping mechanism of glucose favored the generation of peanut-like Au-MTX conjugates with high colloidal stability while the post-capping mechanism of dextran and sucrose resulted in the production of Au-MTX conjugates featuring excellent near-infrared (NIR) optical properties with a long-wavelength plasmon resonance near 630-760 nm. Moreover, in vitro bioassays showed that cancer cell viabilities upon incubation with free MTX, Au-MTX conjugates doped with glucose, dextran and sucrose for 48 h were 74.6%, 55.0%, 62.0%, and 63.1%, respectively. Glucose-doped Au-MTX conjugates exhibited a higher anticancer activity than those doped with dextran and sucrose, therefore potentially presenting a promising treatment platform for anticancer therapy. Based on the present study, this work may provide the first example of using biocompatible sugars as regulating agents to effectively guide the shape and assembly behavior of Au-MTX conjugates. Potentially, the synergistic strategy of drug molecules and sugar molecules may offer the possibility to create more gold-based nanocarriers with new shapes and beneficial features for advanced anticancer therapy.

文章鏈接：

https://www.sciencedirect.com/science/article/pii/S037851731731195X?via%3Dihub