Self-Assembling Doxorubicin Silk Hydrogels for the Focal Treatment of Primary Breast Cancer

Abstract

Standard care for early stage breast cancer includes tumor resection and local radiotherapy to achieve long-term remission. Systemic chemotherapy provides only low locoregional control of the disease; to address this, self-assembling silk hydrogels that can retain and then deliver doxorubicin locally are described. Self-assembling silk hydrogels show no swelling, are readily loaded with doxorubicin under aqueous conditions, and release drug over 4 weeks in amounts that can be fine-tuned by varying the silk content. Following successful in vitro studies, locally injected silk hydrogels loaded with doxorubicin show excellent antitumor response in mice, outperforming the equivalent amount of doxorubicin delivered intravenously. In addition to reducing primary tumor growth, doxorubicin-loaded silk hydrogels reduce metastatic spread and are well tolerated in vivo. Thus, silk hydrogels are well suited for the local delivery of chemotherapy and provide a promising approach to improve locoregional control of breast cancer.