Nanorobots Sense Local Physicochemical Heterogeneities of Tumor Matrisome

Abstract:The dissemination of cancer is brought about by continuous interaction of malignantcells with their surrounding tissue microenvironment. Understanding and quantifying the remodelingof local extracellular matrix (ECM) by invading cells can therefore provide fundamental insightsinto the dynamics of cancer dissemination. In this paper, weuse an active and untethered nanomechanical tool, realized as magnetically driven nanorobots, to locally probe a 3D tissue culture microenvironment consisting of cancerous and non-cancerous epithelia, embedded within reconstituted basement membrane(rBM)matrix. Our assay is designed to mimicthe in vivohistopathological milieu of a malignant breast tumor. We find that nanorobots preferentially adhere to the ECM near cancer cells: this isdue to the distinctchargeconditions of the cancer-remodeled ECM. Surprisingly, quantitative measurements estimatethatthe adhesive force increaseswith the metastatic ability of cancer cell lines, while the spatial extent of the remodeled ECM was measured to be approximately 40μm for all cancercell lines studied here. We hypothesized and experimentally confirmedthat specific sialic acid linkages specificto cancer-secreted ECM may be a major contributing factor in determining this adhesive behavior. The findings reported here can lead to promisingapplications in cancer diagnosis, quantification of cancer aggression, invivodrug delivery applications, and establishes the tremendous potential of magnetic nanorobots for fundamental studies of cancer biomechanics.