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Photoactivated Osmium Arene Anticancer Complexes.

Xuling Xue1, Ying Fu2,3, Liang He4

  • 1Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China.

Inorganic Chemistry
|September 10, 2021
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Summary
This summary is machine-generated.

New osmium-arene curcumin complexes show potent photocytotoxicity against cancer cells, including cisplatin-resistant types, with minimal toxicity to normal cells. These complexes offer a promising avenue for photoactivated chemotherapy (PACT).

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Area of Science:

  • Organometallic Chemistry
  • Photochemistry
  • Cancer Therapeutics

Background:

  • Half-sandwich Os-arene complexes show anticancer potential, but their photochemistry is underexplored.
  • Osmium complexes offer unique photophysical properties for targeted therapies.

Purpose of the Study:

  • To investigate the photocytotoxicity and photochemistry of novel Os-arene curcumin and N,N-chelated complexes.
  • To evaluate their potential as photosensitizers for photoactivated chemotherapy (PACT).

Main Methods:

  • Synthesis and characterization of O,O-chelated ([Os(η⁶-p-cymene)(Curc)Cl] and [Os(η⁶-biphenyl)(Curc)Cl]) and N,N-chelated ([Os(η⁶-biphenyl)(dpq)I]PF₆ and [Os(η⁶-biphenyl)(bpy)I]PF₆) complexes.
  • Assessment of photocytotoxicity against various cancer cell lines and normal cells under blue light.
  • Cellular localization studies (mitochondria, nucleus) and investigation of damage mechanisms (DNA, mitochondrial, ROS).
  • Photochemical studies using NMR, HPLC-MS, HERFD, XANES spectroscopy, and theoretical computation.

Main Results:

  • Osmium-arene curcumin complexes exhibited significant photocytotoxicity (blue light IC₅₀: 2.6-5.8 μM, PI = 23-34) against cancer cells, notably cisplatin-resistant ones, while sparing normal cells.
  • Complexes localized in mitochondria in the dark and translocated to the nucleus upon irradiation, causing DNA and mitochondrial damage.
  • Treatment with OsCUR-2 induced apoptosis, ROS generation, DNA damage, and inhibited angiogenesis and colony formation in A549 lung cancer cells.
  • Photochemical studies revealed selective arene ligand photodissociation and Os(II) to Os(III) oxidation under blue light or UVA irradiation.

Conclusions:

  • Osmium-arene curcumin complexes, particularly OsCUR-2, demonstrate potent photocytotoxicity and a favorable safety profile.
  • These complexes induce multiple damage pathways in cancer cells, potentially overcoming cisplatin resistance.
  • The findings highlight OsCUR-2 as a promising candidate for development as a photosensitizer in anticancer PACT.