Metallo-Liposomes of Ruthenium Used as Promising Vectors of Genetic Material

Abstract

Gene therapy is a therapeutic process consisting of the transport of genetic material into cells. The design and preparation of novel carriers to transport DNA is an important research line in the medical field. Hybrid compounds such as metallo-liposomes, containing a mixture of lipids, were prepared and characterized. Cationic metal lipids derived from the [Ru(bpy)3]2+ complex, RuC11C11 or RuC19C19, both with different hydrophobic/lipophilic ratios, were mixed with the phospholipid DOPE. A relation between the size and the molar fraction α was found and a multidisciplinary study about the interaction between the metallo-liposomes and DNA was performed. The metallo-liposomes/DNA association was quantified and a relationship between Kapp and α was obtained. Techniques such as AFM, SEM, zeta potential, dynamic light scattering and agarose gel electrophoresis demonstrated the formation of lipoplexes and showed the structure of the liposomes. L/D values corresponding to the polynucleotide’s condensation were estimated. In vitro assays proved the low cell toxicity of the metallo-liposomes, lower for normal cells than for cancer cell lines, and a good internalization into cells. The latter as well as the transfection measurements carried out with plasmid DNA pEGFP-C1 have demonstrated a good availability of the Ru(II)-based liposomes for being used as non-toxic nanovectors in gene therapy.

Metallo-Liposomes Derived from the [Ru(bpy)3]2+ Complex as Nanocarriers of Therapeutic Agents

“…A K app value of 2.6 × 10 4 g −1 mL −1 was obtained at α = 0.32 from a non-linear fit by using Equation (7). This value agrees with those obtained for metallo-liposomes formed by the doublechained RuC11C11 (or RuC19C19) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) [25], confirming that the binding of the Ru-based liposomes to ct-DNA is mainly due to electrostatic interactions between the cationic head groups of the ruthenium surfactants and the phosphate groups of the nucleic acid.…”

“…A change in DNA circular dichroism spectrum indicates a variat in the secondary structure of the polynucleotide. Figure 5B The lipoplex sizes obtained in this work are similar to those found for liposomes containing the double-chained surfactants RuC11C11 or RuC19C19 and DOPE [25]. On the other hand, similar results are also observed with respect to the ct-DNA condensation: conformational changes in the nucleic acid happen at similar L/D ratios for a given α value, showing no dependence on the type of surfactant forming the metallo-liposomes.…”

“…Recently, unilamellar liposomes of DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine) and metallosurfactant molecules derived from the [Ru(bpy) 3 ] 2+ complex, with two different hydrocarbon tail lengths, were synthesized by our group [25]. Strong interaction with DNA, low toxicity and good internalization into cells were observed for different cell lines.…”

Non-viral Vectors in Gene Therapy: Recent Development, Challenges, and Prospects

“…Lebrón et al . generated cationic metallo-liposomes of Ruthenium (Ru) and phospholipid complexes to increase polycation and enhance transfection ( 67 ). They also discovered that transfection was impacted by the length of the Ru-lipid and hydrophobicity.…”

Ruthenium-based antitumor drugs and delivery systems from monotherapy to combination therapy

“…López-Cornejo et al 136 formulated derived cationic metal ruthenium complexes with DOPE to deliver genetic material in gene therapy.…”