Contents lists available at ScienceDirect Journal of Inorganic Biochemistry journal homepage: www.elsevier.com/locate/jinorgbio Ruthenium dendrimers as carriers for anticancer siRNA Sylwia Michlewska a,b , Maksim Ionov b, ⁎ , Marta Maroto-Díaz c,d , Aleksandra Szwed b , Aliaksei Ihnatsyeu-Kachan e , Svetlana Loznikova e , Dzmitry Shcharbin e , Marek Maly f , Rafael Gomez Ramirez c,d , Francisco Javier de la Mata c,d , Maria Bryszewska b a Laboratory of Microscopic Imaging and Specialized Biological Techniques, Faculty of Biology and Environmental Protection, University of Lodz, Banacha12/16, 90-237 Lodz, Poland b Department of General Biophysics, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland c Departamento Química Orgánica y Química Inorganica, Universidad de Alcala de Henares, Spain d Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain e Institute of Biophysics and Cell Engineering of NASB, Akademicheskaja 27, Minsk 220072, Belarus f Department of Physics, Faculty of Science, J. E. Purkinje University in Ústí nad Labem, Ústí nad Labem, Czech Republic ARTICLE INFO Keywords: Dendrimer Ruthenium siRNA Drug delivery Computer modeling Molecular dynamics ABSTRACT Dendrimers, which are considered as one of the most promising tools in the field of nanobiotechnology due to their structural organization, showed a great potential in gene therapy, drug delivery, medical imaging and as antimicrobial and antiviral agents. This article is devoted to study interactions between new carbosilane-based metallodendrimers containing ruthenium and anti-cancer small interfering RNA (siRNA). Formation of com- plexes between anti-cancer siRNAs and Ru-based carbosilane dendrimers was evaluated by transmission electron microscopy, circular dichroism and fluorescence. The zeta-potential and the size of dendriplexes were de- termined by dynamic light scattering. The internalization of dendriplexes were estimated using HL-60 cells. Results show that ruthenium dendrimers associated with anticancer siRNA have the ability to deliver siRNA as non-viral vectors into the cancer cells. Moreover, dendrimers can protect siRNA against nuclease degradation. Nevertheless, further research need to be performed to examine the therapeutic potential of ruthenium den- drimers as well as dendrimers complexed with siRNA and anticancer drugs towards cancer cells. 1. Introduction In normal cells, regulation of apoptosis is controlled by the synthesis of anti-apoptotic B-cell lymphoma 2 (Bcl-2) proteins [1,2]. One of the characteristics of cancer cells is enhanced synthesis of these Bcl-2 fa- mily proteins [3]. Neoplastic cells lose the ability to regulate apoptosis. Transfection into cancer cells of siRNAs complementary to the anti- apoptotic proteins, Bcl-xL, Bcl-2, Bcl-W, Mcl-xl (myeloid cell leukemia protein) and Bcl-B, is possible. It can lead to inhibition of their synthesis by an interference process [1,2,4,5] The serious limitation of such treatment is the effective delivery of siRNAs to cancer cells [6]. Due to the negative charge of siRNAs, they cannot effectively cross the plasma membrane. An additional problem is the possible degradation of nucleic acid by endonucleases before the start of the interference process [3]. Using nanomaterials as transfection vehicles for siRNAs can sig- nificantly improve nucleic acid internalization into cancer cells. Such nanocarriers should be positively charged, monodispersed and non- toxic to normal cells. Among a wide range of polymeric drug carriers that can be used in nanomedicine, dendrimers are the most promising nanoparticles, due their size, surface charge and solubility in water. Some of dendrimers can be used in therapy of HIV, cancers and genetic diseases [7–10]. The possibility of using dendrimers in gene silencing has been intensively studied [11]. Complexes of siRNAs with dendrimers can protect them from de- gradation by RNases [12]. Moreover, such complexes are positively charged [13,14], which allows them to interact easily with negatively charged cell membranes and enter cells by endocytosis [14]. Dendrimers are synthesized in a controlled manner. They consist of a core and attached repetitive units (branches) in the form of successive layers that create increasingly higher generations [7,13,15]. There are functional groups at the ends of branches that can be connected to substituents. The presence of surface groups determines dendrimer properties, such as a shape, size and charge [13]. Dendrimers are monodispersive and stable [1]. Due to the large number of charged end groups, they can form complexes with nucleic acids [16–18]. They can enter cells without damaging them [5]. Different types of dendrimers https://doi.org/10.1016/j.jinorgbio.2018.01.001 Received 20 September 2017; Received in revised form 29 December 2017; Accepted 7 January 2018 ⁎ Corresponding author at: Department of General Biophysics, University of Lodz, Pomorska st. 141/143, Lodz 90-236, Poland. E-mail address: maksion@biol.uni.lodz.pl (M. Ionov). Journal of Inorganic Biochemistry 181 (2018) 18–27 Available online 12 January 2018 0162-0134/ © 2018 Elsevier Inc. All rights reserved. T