We report the design, synthesis, and in vitro evaluation of stimuli-responsive nanoscale micelles that can be activated by light to induce a cytotoxic effect. Micelles were assembled from amphiphilic units made of a photoactivatable ferrocenyl linker, connected on one side to a lipophilic chain, and on the other side to a hydrophilic pegylated chain. In vitro experiments indicated that pristine micelles ("off" state) were nontoxic to MCF-7 cancer cells, even at high concentrations, but became potent upon photoactivation ("on" state). The illumination process led to the dissociation of the micelles and the concomitant release of iron species, triggering cytotoxicity.

• Klíčová slova
• cancer, ferrocene, micelles, nanomedicine, oxidative stress, phototherapy,
• MeSH
• fototerapie MeSH
• metaloceny farmakologie   MeSH
• micely * MeSH
• protinádorové látky * MeSH
• železnaté sloučeniny * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ferrocene MeSH Prohlížeč
• metaloceny MeSH
• micely * MeSH
• protinádorové látky * MeSH
• železnaté sloučeniny * MeSH

Tumor-specific drug delivery is a major challenge for the pharmaceutical industry. Nanocarrier systems have been widely investigated to increase and control drug delivery to the heterogeneous tumor microenvironment. Classically, the uptake of nanocarriers by solid tumor tissues is mainly mediated by the enhanced permeability and retention effect (EPR). This EPR effect depends on the tumor type, its location, the physicochemical properties of the carriers, and the blood perfusion of the tumoral lesions. The main goal of this study was to evaluate in vivo tumor uptake of micelle carriers, assisted by microbubble/ultrasound sonoporation. Micelles were tracked using bi-modal imaging techniques to precisely localize both the nanocarrier and its payload. Micelles were loaded with a near infrared fluorophore and radiolabeled with zirconium-89. Their pharmacokinetics, biodistribution and passive tumor targeting properties were evaluated in a subcutaneous glioblastoma (U-87 MG) mouse model using optical and PET imaging. Finally, accumulation and diffusion into the tumor micro-environment was investigated under microbubble-assisted sonoporation, which helped homogenize the delivery of the micelles. The in vivo experiments showed a good correlation between optical and PET images and demonstrated the stability of the micelles in biological media, their high and long-term retention in the tumors and their clearance through the hepato-biliary pathway. This study demonstrates that bi-modal imaging techniques are powerful tools for the development of new nanocarriers and that sonoporation is a promising method to homogenize nanomedicine delivery to tumors.

• MeSH
• gliom * diagnostické zobrazování   MeSH
• lékové transportní systémy metody   MeSH
• micely * MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádorové mikroprostředí MeSH
• nosiče léků chemie   MeSH
• pozitronová emisní tomografie MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• micely * MeSH
• nosiče léků MeSH