^aInstitute of Organic Synthesis and Photoreactivity �Italian National Research Council, Via P. Gobetti, 101, 40129 Bologna, Italy

^bInstitute of Microelectronics and Microsystems �Italian National Research Council, Via P. Gobetti, 101, 40129 Bologna, Italy

^cDipartimento di Biotecnologie e Scienze della Vita (DBSV), Università degli Studi dell'Insubria, via Dunant 3, Varese, Italy

摘要９�/span>Doxorubicin is one of the most effective chemotherapeutic agents for the treatment of several neoplastic conditions, such as leukemia, neuroblastoma, soft tissue and bone sarcomas, breast cancer, ovarian cancer and others. However, its clinical application is limited by cardiotoxicity, such as cardiomyopathy, that once developed carries a poor prognosis and is frequently fatal. The controlled release of doxorubicin by means of a smart carrier is a strategy to overcome the aforementioned drawback. Herein, doxorubicin/keratin nanoparticles were prepared by loading the drug through ionic gelation and aggregation methods, without using cross linkers, organic solvents neither surfactants. Both methodologies afford nanoparticles with yields up to 100�?span style="font-family:times new roman;">wt%, depending on the loading amount of doxorubicin. Although aggregation yield smaller nanoparticles (≇�/span>100�?span style="font-family:times new roman;">nm), ionic gelation allows a higher drug loading (up to 30�?span style="font-family:times new roman;">wt%,). More importantly, nanoparticles obtained through this procedure display a pH-responsive release of the drug: indeed Peppas-Salhin model suggests that, the doxorubicin release mechanism is predominantly controlled by diffusion at pH�?span style="font-family:times new roman;">7.4 and by protein swelling at pH�?span style="font-family:times new roman;">5.

Moreover, nanoparticles prepared by ionic gelation resulted in more efficient cell killing of MDA-MB-231 and MCF-7 breast cancer cells than those prepared by aggregation. Based on the herein presented preliminary results, ionic gelation emerges as a promising approach for the preparation of keratin-based doxorubicin nanocarriers for cancer therapy, that is worth to further investigate.