Tufts University, Department of Biomedical Engineering, 4 Colby Street, Medford, MA 02155, USA.
Biomaterials. 2012 Nov;33(33):8442-50. doi: 10.1016/j.biomaterials.2012.08.004. Epub 2012 Aug 24.
Breast cancer is the most common of all malignant diseases in women. Systemic chemotherapy provides low clinical benefit for locoregional control of the disease, while localised chemotherapy may provide a therapeutic advantage. In this study, doxorubicin-loaded silk films were directly applied to tumours. Affinity binding studies demonstrated that the adsorption of doxorubicin onto silk was partially dependent on crystallinity. By manipulating silk crystallinity, or β-sheet content, the doxorubicin release rate could be controlled ranging from immediate release to prolonged release over >4 weeks. The therapeutic impact of doxorubicin-loaded silk films on primary tumour growth and metastasis was assessed in mice using a humanised orthotopic breast cancer model (adenocarcinoma). Both soluble and stabilised silk films loaded with doxorubicin had a significantly greater primary tumour response than the equivalent dose of doxorubicin administered intravenously in the absence of the silk film carrier. In addition to reducing primary tumour growth, stabilised silk films loaded with doxorubicin also reduced metastatic spread and autopsy indicated that these films were not associated with any local or systemic toxicities. Collectively, these results suggest that the future use of this approach for localised chemotherapy is promising.
乳腺癌是女性中最常见的恶性疾病。全身化疗对局部控制疾病的临床获益较低，而局部化疗可能提供治疗优势。在这项研究中，载阿霉素的丝膜直接应用于肿瘤。亲和结合研究表明，阿霉素吸附到丝上部分依赖于结晶度。通过操纵丝的结晶度或β-折叠含量，可以控制阿霉素的释放速率，从即刻释放到超过 4 周的缓释。在使用人源化原位乳腺癌模型（腺癌）的小鼠中，评估了载阿霉素的丝膜对原发性肿瘤生长和转移的治疗影响。载有阿霉素的可溶性和稳定丝膜的原发性肿瘤反应明显大于静脉内给予相当于丝膜载体的阿霉素的剂量。除了减少原发性肿瘤生长外，载有阿霉素的稳定丝膜还减少了转移扩散，尸检表明这些膜与任何局部或全身毒性无关。总的来说，这些结果表明，这种局部化疗的方法具有广阔的应用前景。
