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Nanorobots Sense Local Physiochemical Heterogeneities of Tumor Matrisome

preprint
submitted on 02.04.2020 and posted on 03.04.2020 by Debayan Dasgupta, Dharma Pally, Deepak K. Saini, Ramray Bhat, Ambarish Ghosh
The dissemination of cancer is brought about by continuous interaction of malignant cells with their surrounding tissue microenvironment. Understanding and quantifying the remodeling of local extracellular matrix (ECM) by invading cells can therefore provide fundamental insights into the dynamics of cancer dissemination. In this paper, we use 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 mimic the in vivo histopathological milieu of a malignant breast tumor. We find that nanorobots preferentially adhere to the ECM near cancer cells: this is due to the distinct charge conditions of the cancer-remodeled ECM. Surprisingly, quantitative measurements estimate that the adhesive force increases with the metastatic ability of cancer cell lines, while the spatial extent of the remodeled ECM was measured to be approximately 40 μm for all cancer cell lines studied here. We hypothesized and experimentally confirmed that specific sialic acid linkages specific to cancer-secreted ECM may be a major contributing factor in determining this adhesive behavior. The findings reported here can lead to promising applications in cancer diagnosis, quantification of cancer aggression, in vivo drug delivery applications, and establishes the tremendous potential of magnetic nanorobots for fundamental studies of cancer biomechanics.

Funding

SERB ECR Grant (1586)

Wellcome Trust-DBT India Alliance Fellowship (WELT0041)

DBT IISc Partnership Program Phase II at IISc BT/PR27952/INF/22/212/2018

Department of Biotechnology

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History

Email Address of Submitting Author

dharmapally@iisc.ac.in

Institution

Indian Institute of Science

Country

India

ORCID For Submitting Author

0000-0003-4814-8875

Declaration of Conflict of Interest

No conflict of interest

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