Satpathy Minati, Wang Liya, Zielinski Rafal, Qian Weiping, Lipowska Malgorzata, Capala Jacek, Lee Gee Young, Xu Hong, Wang Y Andrew, Mao Hui, Yang Lily
Emory University School of Medicine, Atlanta, GA, USA.
Small. 2014 Feb 12;10(3):544-55. doi: 10.1002/smll.201301593. Epub 2013 Aug 27.
Despite advances in cancer diagnosis and treatment, ovarian cancer remains one of the most fatal cancer types. The development of targeted nanoparticle imaging probes and therapeutics offers promising approaches for early detection and effective treatment of ovarian cancer. In this study, HER-2 targeted magnetic iron oxide nanoparticles (IONPs) are developed by conjugating a high affinity and small size HER-2 affibody that is labeled with a unique near infrared dye (NIR-830) to the nanoparticles. Using a clinically relevant orthotopic human ovarian tumor xenograft model, it is shown that HER-2 targeted IONPs are selectively delivered into both primary and disseminated ovarian tumors, enabling non-invasive optical and MR imaging of the tumors as small as 1 mm in the peritoneal cavity. It is determined that HER-2 targeted delivery of the IONPs is essential for specific and sensitive imaging of the HER-2 positive tumor since we are unable to detect the imaging signal in the tumors following systemic delivery of non-targeted IONPs into the mice bearing HER-2 positive SKOV3 tumors. Furthermore, imaging signals and the IONPs are not detected in HER-2 low expressing OVCAR3 tumors after systemic delivery of HER-2 targeted-IONPs. Since HER-2 is expressed in a high percentage of ovarian cancers, the HER-2 targeted dual imaging modality IONPs have potential for the development of novel targeted imaging and therapeutic nanoparticles for ovarian cancer detection, targeted drug delivery, and image-guided therapy and surgery.
尽管癌症诊断和治疗取得了进展，但卵巢癌仍然是最致命的癌症类型之一。靶向纳米颗粒成像探针和治疗方法的发展为卵巢癌的早期检测和有效治疗提供了有前景的途径。在本研究中，通过将一种高亲和力、小尺寸且用独特近红外染料（NIR-830）标记的HER-2亲和体与纳米颗粒偶联，开发了HER-2靶向磁性氧化铁纳米颗粒（IONPs）。使用临床相关的原位人卵巢肿瘤异种移植模型，结果表明HER-2靶向IONPs被选择性地递送至原发性和播散性卵巢肿瘤中，能够对腹腔中低至1毫米的肿瘤进行非侵入性光学和磁共振成像。确定IONPs的HER-2靶向递送对于HER-2阳性肿瘤的特异性和灵敏成像至关重要，因为在将非靶向IONPs全身递送至携带HER-2阳性SKOV3肿瘤的小鼠后，我们无法在肿瘤中检测到成像信号。此外，在全身递送HER-2靶向IONPs后，在HER-2低表达的OVCAR3肿瘤中未检测到成像信号和IONPs。由于HER-2在高比例的卵巢癌中表达，HER-2靶向双模态成像IONPs具有开发用于卵巢癌检测、靶向药物递送以及图像引导治疗和手术的新型靶向成像和治疗纳米颗粒的潜力。
