Pharmaceutics & Novel Drug Delivery Systems

Biography

Biography: Serena Mazzucchelli

Abstract

Chemotherapeutic treatment of breast cancer is based on maximum tolerated dose (MTD) approach. This strategy, however, presents several disadvantages, including prolonged time intervals between treatment cycles and development of therapeutic resistance. However, advanced stage tumors are not effectively eradicated by MTD owing to suboptimal drug targeting, onset of therapeutic resistance and neoangiogenesis. In contrast, “metronomic” chemotherapy is based on frequent but lower dose drug administrations, resulting in neovascularization inhibition and induction of tumor dormancy.[1] For this reason, metronomic chemotherapy is now envisaged as an interesting alternative for either primary systemic therapy or maintenance therapy. However, low drug accumulation at the tumor and poor effectiveness against highly aggressive metastatic cancer limit the applicability. Here we show the potential of H-ferritin (HFn)-mediated targeted nanodelivery of metronomic doxorubicin (DOX) in the setting of a highly aggressive and metastatic 4T1 breast cancer mouse model with DOX-inducible expression of chemoresistance.We find that HFn-DOX administered at repeated doses of 1.24 mg kg−1 strongly improves the antitumor potential of DOX chemotherapy arresting the tumor progression. We find that such a potent antitumor effect is attributable to multiple nanodrug action beyond cell killing, including inhibition of tumor angiogenesis and controlling the rise of chemoresistance. Multiparametric assessment of heart tissues, including histology, ultrastructural analysis of tissue morphology, and measurement of markers of ROS, provided evidence that metronomic HFn-DOX allowed us to overcome cardiotoxicity. In conclusion, our results suggest that HFn-DOX has potential for the development of novel nanometronomic chemotherapy for the next generation of safe and personalized oncological treatments.