Mazzucchelli Serena
Luigi Sacco University Hospital, Italy
Title: Nanocages for self-triggered nuclear delivery of Doxorubicin at cancer cells
Biography
Biography: Mazzucchelli Serena
Abstract
Engineered apoferritin nanoparticle (HFn) was developed to achieve a cumulative self-triggered nuclear delivery of antitumor drugs in cancer cells (CC) with subcellular precision. Th e rationale of our approach is based on exploiting the natural arsenal of defense of CC to stimulate them to recruit large amounts of HFn loaded with doxorubicin (DOX) inside their nucleus in response to a noxious stimuli, which leads to decrease of viability and cell death. Aft er demonstrating the selectivity of HFn for representative cancer cells compared to healthy fi broblasts, DOX-loaded HFn were used in CC treatment. Our results proved that loading of DOX in HFn increased the nuclear delivery of the drug, thus enhancing DOX effi cacy. DOXloaded HFn acts as a “Trojan Horse”: HFn were internalized in CC more effi ciently compared to free DOX, then promptly translocated into the nucleus following to the DNA damage caused by the partial release in the cytoplasm of encapsulated DOX. Th is self-triggered translocation allowed the drug release directly in the nuclear compartment, where it exerted its toxic action probably bypassing the action of the Glycoprotein-P. Th is approach was reliable and straightforward providing an antiproliferative eff ect with high reproducibility. Th e particular self-assembling nature of HFn nanocage makes it a versatile and tunable nanovector for a broad raange of molecules suitable both for detection and treatment of CC.
