<p>Recently, the development of dimeric nanoparticles has attracted much attention from researchers, since these materials make it possible to combine various properties and functions in one system. Dumbbell nanoparticles enable the integration of various components to achieve dual functionality, for example imaging and therapy. In our work, we showed that «dumbbell» type magnetite-gold dimeric nanoparticles could be used for combining Cy5 fluorophore and bacteriopheophorbide based photosensitizer for the joint use in fluorescent diagnostics and photodynamic therapy, allowing to avoid the FRET effect. Surface modification of magnetite surface by DOPAC and PEG allows selective photosensitizer binding, whereas disulfide derivative of Cy5 fluorophore was conjugated to gold surface, providing sterical separation of chromophores, thus minimizing FRET effect, and providing colloidal stability in water solutions. Nanoparticles, containing a pair of chromophores can be internalized by CT26 colon cancer cells and fluorophore and photosensitizer fluorescent signals were colocalized in cells cytoplasm and perinuclear area. Cytotoxicity tests have shown no significant negative effects on CT26 cells in vitro at concentrations up to 100&#xa0;µg/mL. Finally, light induced toxicity in time dependent manner was shown. Proposed approach opens new opportunities for simultaneous fluorescent diagnostics and photodynamic therapy of tumors for photosensitizers with low intrinsic fluorescence.</p>

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Dimeric magnetic dumbbell nanoparticles with selective immobilization of chromophores for improved tumor theranostics

  • Iuliia Chudosai,
  • Petr Ostroverkhov,
  • Ekaterina Plotnikova,
  • Kseniya Stepanova,
  • Nelly Chmelyuk,
  • Elizaveta Ivanova,
  • Mihail A. Grin,
  • Olga Fedorova,
  • Natalia Klyachko,
  • Vladimir P. Chekhonin,
  • Maxim Abakumov

摘要

Recently, the development of dimeric nanoparticles has attracted much attention from researchers, since these materials make it possible to combine various properties and functions in one system. Dumbbell nanoparticles enable the integration of various components to achieve dual functionality, for example imaging and therapy. In our work, we showed that «dumbbell» type magnetite-gold dimeric nanoparticles could be used for combining Cy5 fluorophore and bacteriopheophorbide based photosensitizer for the joint use in fluorescent diagnostics and photodynamic therapy, allowing to avoid the FRET effect. Surface modification of magnetite surface by DOPAC and PEG allows selective photosensitizer binding, whereas disulfide derivative of Cy5 fluorophore was conjugated to gold surface, providing sterical separation of chromophores, thus minimizing FRET effect, and providing colloidal stability in water solutions. Nanoparticles, containing a pair of chromophores can be internalized by CT26 colon cancer cells and fluorophore and photosensitizer fluorescent signals were colocalized in cells cytoplasm and perinuclear area. Cytotoxicity tests have shown no significant negative effects on CT26 cells in vitro at concentrations up to 100 µg/mL. Finally, light induced toxicity in time dependent manner was shown. Proposed approach opens new opportunities for simultaneous fluorescent diagnostics and photodynamic therapy of tumors for photosensitizers with low intrinsic fluorescence.