Stimuli-Responsive Mesoporous Silica NPs as Non-viral Dual siRNA/Chemotherapy Carriers for Triple Negative Breast Cancer  Behrad Darvishi, Leila Farahmand, Keivan Majidzadeh-A  Molecular Therapy - Nucleic Acids  Volume 7, Pages 164-180 (June 2017) DOI: 10.1016/j.omtn.2017.03.007 Copyright © 2017 The Author(s) Terms and Conditions

Figure 1 RNAi Induced by siRNA At the beginning of RNA interference process, through the activity of specific nucleases known as Dicers, siRNAs are transferred to specific ribonucleoprotein complexes referred to as RISCs. Transfer of siRNAs results in activation of RISCs, which, in turn, by means of an RNA helicase enzyme, induces unrolling of the double-stranded fragments. The antisense strand, in the next step, guides the RISC-siRNA complex to the complementary target mRNA. Finally, as the complex binds with the complementary mRNA, endonucleases in the RISC complex initiate the degradation process which is then continued by endonucleases in the cytosol, resulting in complete degradation of mRNAs complementary to the siRNA. Molecular Therapy - Nucleic Acids 2017 7, 164-180DOI: (10.1016/j.omtn.2017.03.007) Copyright © 2017 The Author(s) Terms and Conditions

Figure 2 The Fate of MSNs in Cells After internalization, MSN-NPs are translocated to sorting endosomes. In next step, part of the sorting endosomes turn back to the cell’s exterior, and the remaining shift into secondary endosomes that are then fused with lysosomes. Modified MSNs effectively evade endolysosomes and enter the cytosolic compartment, where their cargos are released, and the RNAi process is begun. Molecular Therapy - Nucleic Acids 2017 7, 164-180DOI: (10.1016/j.omtn.2017.03.007) Copyright © 2017 The Author(s) Terms and Conditions

Figure 3 Conventional Stimulus-Responsive Capped MSNs Molecular Therapy - Nucleic Acids 2017 7, 164-180DOI: (10.1016/j.omtn.2017.03.007) Copyright © 2017 The Author(s) Terms and Conditions

Figure 4 New-Generation MSNs Molecular Therapy - Nucleic Acids 2017 7, 164-180DOI: (10.1016/j.omtn.2017.03.007) Copyright © 2017 The Author(s) Terms and Conditions