Near-infrared light-mediated photoactivation of a platinum antitumor prodrug and simultaneous cellular apoptosis imaging by upconversion-luminescent nanoparticles

Angew Chem Int Ed Engl. 2014 Jan 20;53(4):1012-6. doi: 10.1002/anie.201308834. Epub 2013 Dec 6.

Abstract

Platinum-based drugs are among the most active antitumor reagents in clinical practice; their application is limited by side effects and drug resistance. A novel and personalized near-infrared (NIR) light-activated nanoplatform is obtained by combining a photoactivatable platinum(IV) prodrug and a caspase imaging peptide conjugated with silica-coated upconversion-luminescent nanoparticles (UCNPs) for the remote control of antitumor platinum prodrug activation, and simultaneously for real-time imaging of apoptosis induced by activated cytotoxicity. Upon NIR light illumination, the Pt(IV) prodrug complex is activated at the surface of the nanoparticle and active components are selectively released which display cytotoxicity against human ovarian carcinoma A2780 cells and its cisplatin-resistant variant A2780cis cells. More importantly, the caspases enzymes triggered by cytotoxicity would effectively cleave the probe peptide, thereby allowing the direct imaging of apoptosis in living cells.

Keywords: apoptosis; cellular imaging; drug design; nanoparticles; platinum(IV) antitumor prodrugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Fluorescent Dyes / chemistry*
  • Humans
  • Infrared Rays
  • Luminescence*
  • Molecular Structure
  • Nanoparticles / chemistry*
  • Organoplatinum Compounds / chemistry
  • Organoplatinum Compounds / pharmacology*
  • Photochemical Processes
  • Prodrugs / chemistry
  • Prodrugs / pharmacology*
  • Silicon Dioxide / chemistry
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Fluorescent Dyes
  • Organoplatinum Compounds
  • Prodrugs
  • Silicon Dioxide