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Liposomal Delivery of Cell Impermeable Phototoxic Ru(II) Complexes.

David Cullinane1, Karmel Sofia Gkika1, Surajit Ghosh1,2

  • 1School of Chemical Sciences, National Centre for Sensor Research, Dublin City University, Dublin, Ireland.

Chembiochem : a European Journal of Chemical Biology
|March 27, 2026
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Summary

Photoactive ruthenium complexes show promise for cancer therapy but struggle with cell entry. Encapsulating these drugs in peptide-decorated liposomes successfully delivered them into cells, enabling light-activated cancer cell death.

Keywords:
cell impermeableliposomal deliveryruthenium(II) complexes

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Area of Science:

  • Coordination Chemistry
  • Photochemistry
  • Nanomedicine

Background:

  • Photoactive ruthenium polypyridyl complexes offer potential for cancer imaging and therapy due to unique photophysical properties.
  • However, poor cell membrane permeability limits their clinical application, especially for oxygen-dependent therapies in hypoxic tumors.

Purpose of the Study:

  • To develop an effective delivery strategy for cell-impermeable photoactive ruthenium (Ru) (II) complexes.
  • To investigate the cellular uptake, localization, and photocytotoxicity of Ru(II)-phendione complexes encapsulated in peptide-decorated liposomes.

Main Methods:

  • Synthesis of novel trisheteroleptic Ru(II) complexes with the phendione ligand.
  • Encapsulation of Ru(II)-phendione complexes into octaarginine peptide (R8)-decorated liposomes (peptidoliposomes).
  • Characterization of peptidoliposome size, surface charge, and complex retention; assessment of cellular uptake, localization, and photocytotoxicity in A549 and HeLa cells.

Main Results:

  • High encapsulation efficiency (circa 68%) achieved for Ru(II)-phendione complexes within R8-liposomes, forming stable nanoparticles (185-194 nm) with positive surface charge (+23 mV).
  • Cellular uptake and localization of the encapsulated complexes were cell-type dependent, with distinct patterns observed in A549 and HeLa cells.
  • The Ru2-phendione lipoplex demonstrated significant light-induced photocytotoxicity in HeLa cells.

Conclusions:

  • Peptide-decorated liposomes are an effective delivery system for cell-impermeable Ru(II) metallodrugs.
  • This strategy overcomes membrane permeation barriers, enabling photodynamic therapy applications.
  • The cell-type-dependent uptake highlights the complexity of nanoparticle-cell interactions.