Cervical cancer caused by infection with high-risk human papillomavirus remains to be the most deadly gynecologic malignancy worldwide. It is well documented that persistent expression of two oncogenes (E6/E7) plays the key roles in viral-induced cancers. Thus, in vivo detection of the oncoproteins is very important for early diagnosis and prevention of the cancer, especially, the invasive cancer. Recently, affibody molecules have been demonstrated to be a powerful targeting probe for tumor–targeted imaging and diagnosis.
In this study, four HPV16 E7-binding affibody molecules (ZHPV16E7:127, ZHPV16E7:301, ZHPV16E7:384 and ZHPV16E7:745) were screened from a phage-displayed peptide library and used for molecular imaging in tumor-bearing mice.
Biosensor binding analyses showed first that the four affibody molecules bound to HPV16E7 with very high affinity and specificity. They co-localized with E7 protein only in two HPV16-positive cancer cells (SiHa and CaSki). Furthermore, affibody ZHPV16E7:384 was conjugated with Dylight755 and used for in vivo tumour-imaging. Strongly high-contrast tumor retention of this affibody only occurred in HPV16-derived tumors of mice as early as 30 min post-injection, not in HPV-negative and HPV18-derived tumors. The accumulation of Dylight755-conjugated ZHPV16E7:384 in tumor was achieved over a longer time period (24 h).
The data provide strong evidence that E7-specific affibody molecules have great potential used for molecular imaging and diagnosis of HPV-induced cancers.
This work was supported by the National Nature Science Foundation of China (81172463), the Zhejiang Provincial Natural Science Foundation of China (LY15H190009) and Wenzhou Science and Technology Bureau of China (Y20140659).