Cancer is a serious threat to human health and life. With the advent of the era of precision medicine, early screening and molecular targeted therapy through tumor molecular markers have become the key to research. Among them, it has great potential to use bioactive molecules as specific recognition elements for highly sensitive detection and precise location of tumors. Polypeptide probe has the characteristics of good selectivity, low immunogenicity, good biocompatibility, strong penetrability, easy excretion and clearance. It shows strong advantages in cancer diagnosis and even has the trend of replacing the traditional antibody diagnostic and therapeutic reagents.

Recently, the National Center for nanoscience and the research team of Stanford University Department of chemistry have worked together to use peptide molecular probes to achieve the rapid metabolism of tumor targeted molecular diagnosis. First of all, a novel targeted peptide CP for tumor stem cell marker CD133 was obtained by microarray high-throughput screening. The affinity dissociation constant KD of CP and CD133 reached nm level, which was close to the binding force of antibody. Subsequently, they used CP as a target molecule to modify the near-infrared two region (nir-ii) fluorescent molecules for detection. Compared with the common visible light and near-infrared one area fluorescence imaging, the near-infrared two area (detection window is 1000-1700nm) has longer wavelength, lower light scattering and self fluorescence effect of biological tissue, deeper detection depth and higher spatial-temporal resolution.

Figure 1. (a) continuous flow microfluidic chip to achieve high throughput peptide screening; (b) fluorescence molecular "switch" to achieve in-situ affinity identification; (c) new targeted peptide CP screened for tumor stem cell marker CD133 and its molecular binding simulation with CD133.

The researchers prepared a new type of water-soluble nir-ii fluorescent small molecule IRT, which was used for tail vein injection and in vivo tumor imaging through click reaction coupled with CP peptide. Compared with the target free molecules, cp-irt can reach the signal peak in 2 hours. Because most of the fluorescent nanoprobes excrete very slowly in vivo, and remain in liver, spleen and other organs for a long time, which hinders the clinical transformation. However, cp-irt modified by small peptide can be excreted rapidly through kidney and bladder. In contrast, although it has the same targeting effect, the antibody modified IRT is enriched in the liver due to its significantly larger size. In six hours, 90% of cp-irt can be discharged from the body, and in the process of excretion, they used this probe to realize nir-ii fluorescence imaging of ureter for the first time.

Fig. 2. (a) CP modified near-infrared second region fluorescent molecules achieve fast and high-sensitivity imaging of CD133 positive tumors; (b) compared with non targeted fluorescent molecules, the tumor uptake speed and brightness of targeted molecules are significantly improved; (c) small molecule polypeptide modified fluorescent molecules can be rapidly metabolized through the urinary system, while large molecule modified fluorescent molecules such as antibodies stay in the liver; (d) CP- The ureter was imaged by IRT.

This achievement was recently published on advanced materials. The first author of this paper is Wang Weizhi, associate researcher of national nano science center and Ma zhuoran, doctoral student of Stanford University. The corresponding authors are Dai Hongjie, Professor of Stanford University, Liang Yongye, Professor of South University of science and technology and Hu Zhiyuan, researcher of national nano science center. This research is a further expansion of the previous research work of the research group (anal. Chem., 2015, 87, 8367; chem. Commun., 2016, 52, 5690; lab chip, 2015, 15, 4512, etc.).

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Chengdu Shengnuo Biotechnology Co., Ltd. has "Chengdu polypeptide drug engineering technology research center" in Chengdu, mainly engaged in polypeptide, polypeptide drug and beauty peptide research. Our zero defect has passed the FDA certification, and now it has become the first-class professional peptide drug and product development, technology transfer, technical service and peptide drug industry in the scale production and export of China's parks.