Evaluation of fluorophore-tethered platinum complexes to monitor the fate of cisplatin analogs.

Paradigms and Technologies
Methods Development


The platinum drugs cisplatin, carboplatin, and oxaliplatin are highly utilized in the clinic and as a consequence have been extensively studied in the laboratory setting, sometimes by generating fluorophore-tagged analogs. Here, we synthesized two Pt(II) complexes containing ethane-1,2-diamine ligands linked to a BODIPY fluorophore, and compared their biological activity with previously reported Pt(II) complexes conjugated to carboxyfluorescein and carboxyfluorescein diacetate. The cytotoxicity and DNA damage capacity of Pt-fluorophore complexes was compared to cisplatin, and the Pt-BODIPY complexes were found to be more cytotoxic with reduced cytotoxicity in cisplatin-resistant cells. Microscopy revealed a predominately cytosolic localization, with nuclear distribution at higher concentrations. Spheroids grown from parent and resistant cells revealed penetration of Pt-BODIPY into spheroids, and retention of the cisplatin-resistant spheroid phenotype. While most activity profiles were retained for the Pt-BODIPY complexes, accumulation in resistant cells was only slightly affected, suggesting that some aspects of Pt-fluorophore cellular pharmacology deviate from cisplatin.


Jagodinsky, Justin C; Sulima, Agnieszka; Cao, Yiqi; Poprawski, Joanna E; Blackman, Burchelle N; Lloyd, John R; Swenson, Rolf E; Gottesman, Michael M; Hall, Matthew;


  • Antineoplastic Agents/ chemical synthesis
  • Antineoplastic Agents/ chemistry
  • Antineoplastic Agents/ pharmacology
  • Boron Compounds/ chemistry
  • Cell Line, Tumor
  • Cisplatin/ analogs & derivatives
  • Cisplatin/ pharmacology
  • Coordination Complexes/ chemical synthesis
  • Coordination Complexes/ chemistry
  • Coordination Complexes/ toxicity
  • DNA Damage/ drug effects
  • Drug Resistance, Neoplasm/ drug effects
  • Fluorescent Dyes/ chemistry
  • Humans
  • Inhibitory Concentration 50
  • Microscopy, Confocal
  • Platinum/ chemistry
  • Platinum/ toxicity

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