Active Targeting Using HER-2-Affibody-Conjugated Nanoparticles Enabled Sensitive and Specifi c Imaging of Orthotopic HER-2 Positive Ovarian Tumors

作者：Satpathy Minati; Wang Liya; Zielinski Rafal; Qian Weiping; Lipowska Malgorzata; Capala Jacek; Lee Gee Young; Xu Hong; Wang Y Andrew; Mao Hui; Yang Lily^*

来源：Small, 2014, 10(3): 544-555.

DOI：10.1002/smll.201301593

• HER-2 targeted nanoparticles
• HER-2 affibody
• NIR-830 dye
• Optical imaging
• MRI
• orthotopic ovarian tumor model

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.

• 出版日期2014-2