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Universal drug delivery platform for anticancer theranostics based on dumbbell-like Fe3O4-Au nanoparticles
* 1, 2 , 1, 2, 3 , 1, 2
1  Laboratory of Biomedical Nanomaterials, National University of Science and Technology (MISIS), 119049 Moscow, Russia
2  Department of Medical Nanobiotechnology, N.I. Pirogov Russian National Research Medical University, 117997 Moscow, Russia
3  Department of General and Inorganic Chemistry, Mendeleev University of Chemical Technology of Russia, 125047 Moscow, Russia
Academic Editor: Pankaj Vadgama


Anticancer therapy is a significant challenge today. The use of nanocarriers as a promising method can influence the pharmacokinetics and biodistribution of drugs, as well as reduce side effects. Combinations of drugs such as doxorubicin and paclitaxel in certain ratios have been shown to exhibit a synergistic effect, while using drugs simultaneously can reduce the development of resistance and the total administered dose. However, delivering combinations of drugs to tumor cells at a given molar ratio is difficult due to differences in the chemical structure and properties of anticancer drugs (hydrophobicity and charge). In this work, magnetic dumbbell-like Fe3O4-Au nanoparticles (MDNPs) are proposed. Firstly, due to their magnetic properties, MDNPs can be used for magneto-resonance imaging. Secondly, the presence of two chemical surfaces (Fe3O4 and Au) allows us to modify MDNPs with different molecules in order to load two different types of drugs at given ratios. MDNPs were produced through the thermal decomposition of Fe(CO)5 and HAuCl4 in octadecene-1. The size was 14±1 nm for Fe3O4 and 4±1 nm for Au. After that, the Fe3O4 surface of the MDNPs was sequentially coated with 3,4-hydroxyphenylacetic acid, FAM-maleimide modified human serum albumin (HSA), and NH2-PEG-COOH. These nanoparticles were stable in both water and PBS for 30 days and allowed for the loading of cisplatin (cPt, 0,3mg/1mg Fe), doxorubicin (DOX, 0,45mg/1mg Fe), and paclitaxel (PTX, 0,35mg/1mg Fe). The Au surface was modified with HSA that had previously been loaded with a drug to obtain a system with two drugs. As a result, two systems were produced (MDNP-cPt-DOX, with a molar ratio of cPt/DOX 1:1, and MDNP-PTX-DOX, with a molar ratio of PTX/DOX: 1:3). These proved to be comparable with free drugs' synergistic results in terms of their toxicity against the CT26 cell line. To summarize, modified MDNPs can be loaded with different types of drugs, and the Au surface allows for the addition of another drug to achieve a synergistic effect in therapy.

Keywords: dumbbell-like nanoparticles, drug delivery system, magnetic nanoparticles, anticancer therapy