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Engineered Ferritin Nanoparticles for the Bioluminescence Tracking of Nanodrug Delivery in Cancer
Authors:Michela Bellini  Benedetta Riva  Veronica Tinelli  Maria Antonietta Rizzuto  Lucia Salvioni  Miriam Colombo  Francesca Mingozzi  Alberto Visioli  Laura Marongiu  Gianni Frascotti  Michael S. Christodoulou  Daniele Passarella  Davide Prosperi  Luisa Fiandra
Abstract:The identification of a highly sensitive method to check the delivery of administered nanodrugs into the tumor cells is a crucial step of preclinical studies aimed to develop new nanoformulated cures, since it allows the real therapeutic potential of these devices to be forecast. In the present work, the ability of an H‐ferritin (HFn) nanocage, already investigated as a powerful tool for cancer therapy thanks to its ability to actively interact with the transferrin receptor 1, to act as an efficient probe for the monitoring of nanodrug delivery to tumors is demonstrated. The final formulation is a bioluminescent nanoparticle, where the luciferin probe is conjugated on nanoparticle surface by means of a disulfide containing linker (Luc‐linker@HFn) which is subjected to glutathione‐induced cyclization in tumor cell cytoplasm. The prolonged imaging of luciferase+ tumor models, demonstrated by an in vitro and an in vivo approach, associated with the prolonged release of luciferin into cancer cells by disulfide bridge reduction, clearly indicates the high efficiency of Luc‐linker@HFn for drug delivery to the tumor tissues.
Keywords:apoferritin nanoparticles  luciferase/luciferin  nanomedicine  self‐immolative linkers  tumor targeting
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