Milgroom Andrew, Intrator Miranda, Madhavan Krishna, Mazzaro Luciano, Shandas Robin, Liu Bolin, Park Daewon
University of Colorado Denver Anschutz Medical Campus, Department of Bioengineering, Mail Stop 8607, 12700 East 19th Avenue, Aurora, CO 80045, United States.
University of Colorado Denver Anschutz Medical Campus, Department of Pathology, Mail Stop 8104, 12801 East 17th Avenue, Aurora, United States.
Colloids Surf B Biointerfaces. 2014 Apr 1;116:652-7. doi: 10.1016/j.colsurfb.2013.10.038. Epub 2013 Nov 1.
Ultrasound (US) is used widely in the context of breast cancer. While it is advantageous for a number of reasons, it has low specificity and requires the use of a contrast agent. Its use as a standalone diagnostic and real-time imaging modality could be achieved by development of a tumor-targeted ultrasound contrast agent (UCA); functionalizing the UCA with a tumor-targeting agent would also allow the targeted administration of anti-cancer drugs at the tumor site. In this article, clinical US techniques are used to show that mesoporous silica nanoparticles (MSNs), functionalized with the monoclonal antibody Herceptin(®), can be used as an effective UCA by increasing US image contrast. Furthermore, in vitro assays show the successful localization and binding of the MSN-Herceptin conjugate to HER2+ cancer cells, resulting in tumor-specific cytotoxicity. These results demonstrate the potential of MSNs as a stable, biocompatible, and effective therapeutic and diagnostic ("theranostic") agent for US-based breast cancer imaging, diagnosis, and treatment.
超声(US)在乳腺癌领域应用广泛。尽管因其多种原因而具有优势,但它特异性较低且需要使用造影剂。通过开发肿瘤靶向超声造影剂(UCA)可实现其作为独立诊断和实时成像模态的应用;用肿瘤靶向剂对UCA进行功能化修饰还能在肿瘤部位实现抗癌药物的靶向给药。在本文中,临床超声技术用于表明,用单克隆抗体赫赛汀(Herceptin®)功能化的介孔二氧化硅纳米颗粒(MSN)可通过增加超声图像对比度用作有效的UCA。此外,体外试验表明MSN-赫赛汀偶联物成功定位并结合到HER2+癌细胞上,从而产生肿瘤特异性细胞毒性。这些结果证明了MSN作为一种稳定、生物相容且有效的治疗和诊断(“治疗诊断”)剂用于基于超声的乳腺癌成像、诊断和治疗的潜力。