Nanorobots for Rapid Noninvasive Cancer Diagnosis

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Complex transport processes are assisted by dynamic in-situ chemical processes that provide power and control for biomolecular motors in living cells and organisms. These natural processes have been inspiring generations of researchers to develop chemically-powered synthetic micro/nanorobots toward a variety of in vitro and in vivo biomedical applications.1 Micro/nanorobots have shown great promise for executing various demanding biosensing applications toward precise diagnosis of diseases owing to their unique features of autonomous motion, easy surface functionalization, as well as effective capture and isolation of target analytes in unprocessed body fluids.2 A very important application is to isolate and detect circulating tumor cells (CTCs) from cancer patient blood at different stage of disease. CTCs are one kind of tumor cells, shed from primary tumors or metastatic sites into peripheral blood and travel through the bloodstream to distant organs, causing metastasis. Given the fact that CTCs contribute to the spread of cancer and attribute to >80% of cancer-related mortalities, detection and characterization of CTCs could provide convenient prognosis and early determination of progression of the disease. However, detection of CTCs is technically challenging due their rare number (1-100 in 109 blood cells).3,4 From this perspective micro/nanorobots are increasingly being explored for effective capture and isolation of CTCs in shortest possible time.  However, designing micro/nanorobots for practical biomedical applications such as CTCs isolation is highly challenging as miniaturization brings fundamental engineering challenges.

The Magneto-Fluorescent Nanorobots (“MFN”) reported for the first time gives insight in designing of smart nanorobots and its benefits in important biomedical applications such as CTC isolation. The nanobots were prepared by complex coordination and conjugation chemistry to selectively assemble multiple components. The presence of multiple component imparted multifunctionality to the nanorobots such as: autonomous propulsion ability in complex biological fluids, magnetic property for guidance and separation, and ability to selectively isolate cancer cells. The nanorobots propelled with high speed even in complex biological fluid such as blood without any other additives. Furthermore, the autonomous motion helped the nanobots to capture and isolate CTCs rapidly and selectively in just 5 min even in unprocessed blood. The nanorobots were able to capture cancer cell with almost 100% efficiency both in serum and whole blood. With constant motion in the sample and magnetic property due to the presence of Fe3O4 shell on Mg nanoparticle, the nanobots offered major improvements in sensitivity, efficiency and speed in capturing cancer cells. We envision that the nanorobot platform proposed in the work can lead to the development of new medical diagnostic microchips for rapid cancer diagnosis, overcoming the shortcomings of current high-resolution diagnostic methodologies.

 DOI: https://doi.org/10.1038/s42004-021-00598-9

Figure 1. Schematic of the self-propelling MFN and cancer cell capture. Lower left side inset shows the upward moving nanorobot due to generation of H2 bubble. Upper left side inset shows cancer cell captured efficiently by MFN due to continuous motion through the sample thus greatly enhancing the interaction and binding efficiency with cancer cells. Lower right side inset shows the Schematic illustration of multicomponent MFN.

References

  1. Goel, A., Vogel, V. Harnessing Biological Motors to Engineer Systems for Nanoscale Transport and Assembly. Nanotech. 3, 465-475 (2008).
  2. Li, J., Esteban-Fernández de Ávila, B., Gao, W., Zhang, L., Wang, J. Micro/nanorobots for biomedicine: Delivery, Surgery, Sensing, and Detoxification, Robot. 2, eaam6431 (2017)
  3. Chaffer, C. L., Weinberg, R. A. A Perspective on Cancer Cell Metastasis. Science, 331, 1559-64 (2011).
  4. Marx V. Tracking Metastasis And Tricking Cancer. Nature, 494, 133-8 (2013).

Dr. Shashwat Banerjee

Head, Central Research Laboratory, Maharashtra Institute of Medical Education and Research