Cholesterol-based nucleolipid-ruthenium complex stabilized by lipid aggregates for antineoplastic therapy

Area of Science:

• Supramolecular Chemistry
• Materials Science
• Oncology

Background:

• Ruthenium complexes show promise as antineoplastic agents but suffer from degradation.
• Developing stable and effective delivery systems is crucial for ruthenium-based cancer therapies.

Purpose of the Study:

• To design and characterize a novel ruthenium complex (ToThyCholRu) stabilized within liposomes for improved antineoplastic therapy.
• To evaluate the anti-proliferative activity of these ruthenium-containing liposomes against cancer cells.

Main Methods:

• Synthesis of a ruthenium complex linked to a cholesterol-containing nucleolipid (ToThyCholRu).
• Incorporation of ToThyCholRu into POPC liposome bilayers to form stable nanoaggregates.
• Assessment of liposome stability and characterization of the ruthenium complex localization within the bilayer.
• Evaluation of anti-proliferative activity against cancer cells in comparison to a NAMI-A-like complex.

Main Results:

• Stable ruthenium-containing liposomes (nanoaggregates) with up to 15% mole fraction of ToThyCholRu were formed.
• The ruthenium complex was effectively localized within the liposome bilayer, with the metal ion near the headgroups and the steroid moiety in the acyl chain region.
• Ruthenium-containing liposomes exhibited enhanced efficacy in inhibiting cancer cell growth compared to a model NAMI-A-like ruthenium complex.

Conclusions:

• The developed ruthenium-containing liposomes offer a stable and effective platform for antineoplastic drug delivery.
• This approach provides new strategies for designing transition-metal-based supramolecular systems for cancer therapy.
• The findings highlight the potential of lipid-stabilized ruthenium complexes for advanced cancer treatment.