SERS-Based Sensors for Drug Monitoring in a 3D Tumor-Stroma Breast Cancer Model

Drug and therapy discovery against cancer are limited by the default of cellular models able to mimic tumoral growth and tumoral interactions with the environment.¹Conventional 2D cellular models are suboptimal and, therefore, more complex 3D in vitro models are required to have closer conditions to those inside living beings. Moreover, to study cellular behaviour in such three-dimensional environments, sensitive and non-invasive techniques are needed as for example Surface-Enhanced Raman Spectroscopy (SERS) which allows to detect low concentrated metabolites located on or next to metallic nanostructures.²Therefore, incorporating these nanostructures into 3D cellular models would allow for in situ detection of metabolites and biomarkers secreted by tumoral cells. Herein, plasmonic nanoparticles are combined with different hydrogels to obtain hybrid bioinks that could be used for printing sensing materials within a 3D cell model. The main goal of this work is to use the hybrid bioinks to print the sensor inside a decellularized extracellular matrix (dECM) bath containing different cancer cell types to support tumoral cell culture and monitor cell behaviour over time. The tumor compartment of the 3D model comprises MDA-MB-231 cells while the stromal compartment comprises human breast fibroblasts (HBF). Therefore, the tumoral model is first obtained by directly bioprinting the tumor core within a supportive bath of breast dECM containing the stromal cells and then the sensors are printed inside. Preliminary results show that the sensor can be tuned to sense different metabolites in a hydrogel dependent manner. Moreover, 3D printing of the hydrogel-based sensors in tumor-stroma model does not affect the integrity of the system and allows cell growth and spreading overtime.³The distribution of different sensors across the model allows for the spatial and temporal monitoring of antitumoral drug consumption by the different cell populations, using 6-thioguanine as a model drug. Further characterization will involve in situ SERS sensing of cell-secreted metabolites related to tumoral death.<br/><br/>1. L. Hutchinson <i>et al.</i> <i>Nat. Rev. Clin. </i><i>Oncol., </i><b>2011</b>,<i> 8</i>, 189-190.<br/>2. M. Moskovits. <i>Rev. Mod. </i><i>Phys., </i><b>1985</b>,<i> 57</i>, 783-826.<br/>3. P. González-Callejo <i>et al.,</i> <i>ACS Appl. Mater. Interfaces, </i><b>2024</b>,<i> 16,</i> 27151–27163.