Nanomotors Sense Local Physicochemical Heterogeneities in Tumor Microenvironments

The invasion of cancer is brought about by continuous interaction of malignant cells with their surrounding tissue microenvironment. Investigating the remodeling of local extracellular matrix (ECM) by invading cells can therefore provide fundamental insights into the dynamics of cancer progression. In this paper, we use an active and untethered nanomechanical tool, realized as magnetically driven nanomotors, to locally probe a 3D tissue culture microenvironment. We made the surprising observation that nanomotors preferentially adhere to the ECM near cancer cells and magnitude of the adhesive force increased with cell lines of higher metastatic ability. We hypothesized and experimentally confirmed that sialic acid linkage specific to cancer‐secreted ECM makes it differently charged, which determines this adhesive behavior. In an assay consisting of both cancerous and non‐cancerous epithelia, designed to mimic the in vivo histopathological milieu of a malignant breast tumor, we find the nanomotors to preferentially decorate the region around the cancer cells. The findings reported here can lead to promising applications in cancer diagnosis and imaging, quantification of cancer aggression and in vivo drug delivery applications. They also establish the tremendous potential of magnetic nanomotors for fundamental studies of cancer mechanobiology.