Carboxybetaine Methacrylate Oligomer Modified Nylon Wire For Circulating Tumor Cells Capture

Cancer is one of the most challenging health issues our society is facing nowadays. In order to conquer cancer, a mass of treatments have been developed and applied. As our understanding of the complexity and diversity of cancers deepens, the treatments of cancer are evolving from the "one drug fits all" stage to the personalized strategy stage. The personalized treatment requires that doctors not only focus on the cancer where it rose, but also its specific molecular, genetic or immunologic subtype, so that judge and adopt different treatments. Among these methods, CTCs, a new tumor-specific biomarker, make sense due to its ability to provide a profile of patient. CTCs are a kind of rare cell shed from the primary site flowing in the bloodstream. They are the major cause of metastasis and cancer-related death. As the development of interventional medical devices, we hope to design a device that can catch CTCs by remaining in the vein for a period of time instead of drawing blood samples from patients. However, materials used for intervention need to meet the requirement of blood compatibility, which is judged by protein adsorbed on the surfaces. Protein adsorption is the first event that happens during the blood-materials interactions, especially in terms of the proteins such as clotting enzymes and fibrinogen. So modification of materials is essential before use.Based on above backgroud, we explored Nylon for our functional materials as it has been widely used on medical devices. Carboxybetaine Methacrylate(CBMA) was chosen as modified molecular for its specific dual-function:the abundant carboxyl of CBMA not only can improve the hydrophilic of surface, but also can provide location sites of antibody. Using DMAEMA and chloropropionic acid as main raw materials, we explored synthesis method of CBMA successfully. After being formaldehyde dealt with, atomic transfer random polymerization (ATRP) method was chosen to graft zwitterionic CBMA oligomers on Nylon surface. The chemical, physical and biological properties of pristine and modified nylon surface were accessed by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscope and atomic force microscope. The results showed that the surfaces were changed tremendously and CBMA brushes were successfully grafted onto nylon surfaces. The blood compatibility of modified surfaces was accessed by water contact angle, platelet adhesion, protein adsorption and plasma recalcification time determinations. The results show that the blood compatibility of modified surfaces was improved obviously.In this paper, we explored capturing CTCs experiments using modified Nylon sheets surfaces. EpCAM was chosen as specific biomaker because if its overexpression in most carcinomas. SGC7901 cell line was chosen because it can exhibit positive expression on a cell membrane efficiently. After being active by EDC/NHS, the anti-EpCAM antibody was grafted with CBMA on the surfaces. The capturing tests were conducted in CTCs culture medium and whole blood respectively. The SGC7901 tumor cells were stained with DAPI and observed by SEM and fluorescence microscope system. It showed that a mass of CTCs were captured from cell medium and enriched from the whole blood without interference from other blood constituents. The experiment results showed the feasibility of modified Nylon medical device to capturing CTCs.The third part of this paper is the capturing efficiency contrast of ATRP method and KH550 method. KH550 method has been widely used as a mature surface modification technology even for CTCs capture. In theory, ATRP method can graft more effective groups than KH550 method, so will have higher capture efficiency. This chapter from the number of grafted CBMA, number of antibody and eventually number of captured tumor cells, three aspects to demonstrate the capturing efficiency. The number of grafted CBMA was quantitatively and qualitatively accessed by the FITC fluorescence intensity. The number of antibody was quantitatively accessed by absorbance at wavelength of 277 nm recorded by UV spectrophotometer. The number of captured CTCs was counted by fluorescence microscope after being stained. The results showed that ATRP method graft CBMA 2.6 times more than KH550 method, the number of antibody was 2.1 times more, and tumor cells was 5.6 times more than KH550 method. Therefore, choosing ATRP method for surface modification was more conducive to the CTCs capturing.