A novel dual-function polymeric scaffold for cancer drug screening

Cell-based assay has been used as a conventional strategy for discovery of new anti-cancer drugs in pharmaceutical industries. Traditionally, two-dimensional (2D) cell culture based cytotoxicity assays are the most common approaches, despite the fact that they have significant limitations in simulating tissue or organ microenvironment. In comparison, 3-dimensional (3D) cell culture provides a more promising tool for new drug discovery, however, next-generation cell growth monitoring device for 3D cell culture is still challenging. Recent studies have shown the potential of metallic nanoparticle-polymeric composites in biosensing systems. We hypothesize that in a polymer-based 3D-cell culture system, cancer cell growth and the subsequent spheroid formation can cause structural change of the polymer network. With the incorporation of metallic nanoparticles into the polymeric network, electrical conductance change of the 3D-scafold may be monitored to reflect cell growth and spheroid formation. Here, we developed a dual-function polymer scaffold (DPS) by integrating thermosensitive polymers, silver flake-decorated polymers, and gNP-decorated polymers as a biosensor to monitor cancer cell growth. We found that the Triple negative breast cancer stem cell line MDA-MB-231 formed spheroid in DPS. It is notable that the increase of cancer cell numbers during the formation of spheroid was proportional to the change of electrical conductance of the 3D-scafold. Importantly, the results from DPS cell growth monitoring method correlate well with conventional cell counting during 3D cell culture of breast cancer cells. SEM imaging and AFM imaging have confirmed the integration of silver flakes and gold nanoparticles in the DPS. Finally, we demonstrated that the DPS 3D-scafold exhibited robust responses to MDA-MB-436 cells when exposed to 3 nM of paclitaxel (PTX) and docetaxel (DTX), respectively. This dual-function 3D-scaffold, for both cell growth and growth monitoring may have a good potential in drug screening in the future. Note: This abstract was not presented at the meeting. Citation Format: Tianfu Wu, Zuan-Tao Lin. A novel dual-function polymeric scaffold for cancer drug screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2154.