In Vitro Anticancer Properties of Copper Metallodendrimers

Abstract

Newly synthesized carbosilane copper dendrimers (CCD) with chloride and nitrate surface groups seem to be good candidates to be used as gene and drug carriers in anti-cancer therapy, due to their properties such as size and surface charge. Copper attached to the nanoparticles is an important element of many biological processes and recently their anti-cancer properties have been widely examined. Zeta size and potential, transmission electron microscopy (TEM), circular dichroism (CD), analysis of haemolytic activity, and fluorescence anisotropy techniques were used to characterize copper dendrimers. Additionally, their cytotoxic properties toward normal (PBMC) and cancer (1301; HL-60) cells were examined. All tested dendrimers were more cytotoxic against cancer cells in comparison with normal cells.

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

“…Two families of copper (II) metallodendrimers, (G n -[CuCl 2 ] m (n = 0, m = 1; n = 1, m = 4; n = 2, m = 8) and G n -[Cu(ONO 2 ) 2 ] m (n = 0, m = 1; n = 1, m = 4; n = 2, m = 8) ( Figure 1 ), were selected to assess the influence of dendrimer generation and the metal counter-ion (chloride and nitrate) on their ability to form complexes with siRNA and be delivered to cancer cells. These compounds had positive charges in zeta potential measurements, corroborating their ionic nature, with the positive charge on the metal complex and the negative charge on the counterion (chloride and nitrate) [ 15 ]. The siRNAs chosen to carry out the study were Mcl-1 and Bcl-2, which are overexpressed in MCF-7cells.…”

“…A possible cooperativity between Cu(II) metallodendrimers, which are active in a wide panel of cancer cell lines, and pro-apoptotic Mcl-1 or Bcl-2 siRNA, have been studied by MMT assay in MCF-7 cells after 72 h treatment. Previously, we reported the IC 50 values for Cu(II)-systems in MCF-7 [ 21 ] and PBMC [ 15 ] cell line. The G n -[Cu] concentration chosen to carry out the viability assays here was a subtoxic concentration of 3 μM.…”

“…Organometallic complexes of platinum, ruthenium, silver, and copper, among others, have proven to be excellent anticancer agents; many of them have been introduced in different nanoparticles or dendritic systems to increase their bioavailability and improve their therapeutic action [ 14 , 15 , 16 ]. Some of them, such as cationic ruthenium carbosilane dendrimers [ 13 ] or multifunctional selenium nanoparticles [ 17 ] used as siRNA carriers, have a synergistic effect through their combined action.…”

“…The mechanism by which the different copper (II) complexes exert their anti-cancer activity is still unknown. Furthermore, copper compounds are able to induce apoptosis in cancer cells [ 15 ]. Our research group has now shown how the inclusion of copper (II) complex into the carbosilane dendritic skeleton potentiated its anticancer activity in different cancer cell lines (PC-3, HL-60, HeLa), with promising results from both in vitro and in vivo experiments [ 15 , 20 ].…”

“…Furthermore, copper compounds are able to induce apoptosis in cancer cells [ 15 ]. Our research group has now shown how the inclusion of copper (II) complex into the carbosilane dendritic skeleton potentiated its anticancer activity in different cancer cell lines (PC-3, HL-60, HeLa), with promising results from both in vitro and in vivo experiments [ 15 , 20 ]. Copper (II) carbosilane dendrimers have shown an extraordinary interaction with different model cell membranes, such as lecithin liposomes and CTAB micelles [ 21 ].…”