The field of personalized medicine is constantly evolving, and new diagnostic tools are needed to understand an individual patient’s disease state, inform clinical decision-making, and monitor therapeutic response. In previous work at MIT, we developed a nanosensor that can identify tumor-specific enzymatic activity profiles, such as from proteases, a crucial class of enzymes, through localized sampling of the tumor microenvironment.
Our nanosensors are composed of thermosensitive liposomes containing functionalized biomarker substrates that are selectively unveiled at the target site by the heat dissipation of co-encapsulated magnetic nanoparticles (MNPs) in response to the application of an alternating magnetic field. A detection assay is then used to quantify the amount of cleaved marker substrates excreted in the urine, a reading that is directly correlated with specific protease activity in the tumor. The spatiotemporally controlled system has been used to measure in vivo tumor protease activity, revealing differences in enzymatic profiles between two mouse models of human colorectal cancer.
At MML, we continue to explore the potential of these and other concepts to develop micro- and nanosensors and mechanisms to control them and communicate diagnostic signals in a non-invasive and cost-efficient manner. For instance, we are designing protease-responsive ultrasound contrast agents (PRUCAs) that can report protease activity through a change in the nonlinear backscattering signal of incoming acoustic waves. Our goal is to assess local protease activity by administering PRUCAs to patients and applying an ultrasound probe to a body area of interest. Additionally, we are developing nanosensors that detect protease activity, coupled with magnetic detection mechanisms, for in vivo use or as convenient benchtop readout systems.