Photo credit: Scott Eisen/AP Images for HHMI

Principal Investigator Sangeeta Bhatia is the John J. and Dorothy Wilson Professor of Health Sciences and Technology and of Electrical Engineering and Computer Science.

Nanotechnology experts, the Bhatia Laboratory has applied a variety of techniques and materials to characterize metastases and their microenvironments with the goal of improving detection, imaging, and treatment. 

In one approach, the group engineered new metastatic detection agents using ultrasmall gold nanoclusters, which have emerged as agile probes for in vivo imaging, and previously been shown to exhibit exceptional tumor accumulation and efficient renal clearance properties. The researchers harnessed the intrinsic catalytic activity of the gold nanoclusters to produce multifunctional protease nanosensors that engage disease microenvironments to produce a direct, highly sensitive, colorimetric urinary readout of the disease state in less than one hour.

In another example, the Bhatia Laboratory worked with the Gertler group to engineer nanoparticles that exhibit enhanced tumor homing. Specifically, despite the important association of tumor microenvironment acidosis and tumor cell invasion, relatively little is known about which areas within a tumor are acidic and how acidosis influences tumor behavior. A labeled pH-responsive peptide was used to mark acidic regions within tumors, demonstrating that acidic regions were not restricted to hypoxic areas. Instead, acidic regions overlapped with highly proliferative, invasive regions at the tumor-stroma interface, and were also marked by increased expression of matrix metalloproteinases. By incorporating the same pH-responsive peptide, the researchers fabricated nanosensors that exhibit improved tumor-homing behavior and PET-based tumor imaging. In parallel, they have worked to develop nanomaterials that allow both monitoring of metastases and therapy.

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