Copper (II) Metallodendrimers Combined with Pro-Apoptotic siRNAs as a Promising Strategy Against Breast Cancer Cells

Abstract

Cancer treatment with small interfering RNA (siRNA) is one of the most promising new strategies; however, transfection systems that increase its bioavailability and ensure its delivery to the target cell are necessary. Transfection systems may be just vehicular or could contain fragments with anticancer activity that achieves a synergistic effect with siRNA. Cationic carbosilane dendrimers have proved to be powerful tools as non-viral vectors for siRNA in cancer treatment, and their activity might be potentiated by the inclusion of metallic complexes in its dendritic structure. We have herein explored the interaction between Schiff-base carbosilane copper (II) metallodendrimers, and pro-apoptotic siRNAs. The nanocomplexes formed by metallodendrimers and different siRNA have been examined for their zeta potential and size, and by transmission electron microscopy, fluorescence polarisation, circular dichroism, and electrophoresis. The internalisation of dendriplexes has been estimated by flow cytometry and confocal microscopy in a human breast cancer cell line (MCF-7), following the ability of these metallodendrimers to deliver the siRNA into the cell. Finally, in vitro cell viability experiments have indicated effective interactions between Cu (II) dendrimers and pro-apoptotic siRNAs: Mcl-1 and Bcl-2 in breast cancer cells. Combination of the first-generation derivatives with chloride counterions and with siRNA increases the anticancer activity of the dendriplex constructs and makes them a promising non-viral vector.

Metallodrugs in cancer nanomedicine

“…Finally, dendrimers, 272–274 hydrogels 275,276 and MOFs together represent the remaining 15%, whose lower research interest might be attributed to their higher formulation and/or design complexity, and lower biocompatibility, as will be further discussed in the following sections. Although the biomedical interest in MOFs mainly started in 2009, with a study where a Fe( iii )-carboxylate nanoscale MOF was used as a delivery vesicle for a Pt( iv ) anticancer prodrug, 277 only a few publications were reporting the use of MOFs in chemotherapeutic studies before 2015.…”

Enhancing the antibacterial activity of PAMAM dendrimer modified with 1,8‐naphthalimides and its copper complex via light illumination

“…The presence of a N,N‐ dimethylamino substituent at the C‐4 atom in the chromophore system of 1,8‐naphthalimides leads to its polarization and absorption of the dendrimer in the visible spectral region. Dendrimers bioactivity may undergo changes after the complexation with metal ions, due to differences in ligands conformation or in the metal ions nature 24–27 . Copper ions Cu 2+ are part of the important trace elements in living organisms.…”

“…undergo changes after the complexation with metal ions, due to differences in ligands conformation or in the metal ions nature. [24][25][26][27] Copper ions Cu 2+ are part of the important trace elements in living organisms. Тhey are one of the most widely studied complexing agents.…”

Polymeric Dendrimers as Nanocarrier Vectors for Neurotheranostics

“…developed a carbosilane dendrimer with Cu (Cuprum) as terminal groups, which could deliver proapoptotic siRNA [siRNAs‐Mcl‐1 (myeloid cell leukaemia‐1) or siRNAs‐Bcl‐2 (B‐cell lymphoma 2)] into MCF‐7 cells, show an excellent apoptotic effect on human breast cancer cells (≈90% cell death). [ 68 ]…”