Magnetically Actuated Protease Sensors for in Vivo Tumor Profiling
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Author(s)
Schuerle, Simone
Dudani, Jaideep Sunil
Anikeeva, Polina Olegovna
Bhatia, Sangeeta N
Christiansen, Michael Gary
Date Issued
October 2016
Journal
Nano Letters
Publisher
American Chemical Society (ACS)
Citation
Schuerle, Simone et al. “Magnetically Actuated Protease Sensors for in Vivo Tumor Profiling.” Nano Letters 16, 10 (September 2016): 6303–6310 © 2016 American Chemical Society
Version
Author's final manuscript
Abstract
Targeted cancer therapies require a precise determination of the underlying biological processes driving tumorigenesis within the complex tumor microenvironment. Therefore, new diagnostic tools that capture the molecular activity at the disease site in vivo are needed to better understand tumor behavior and ultimately maximize therapeutic responses. Matrix metalloproteinases (MMPs) drive multiple aspects of tumorigenesis, and their activity can be monitored using engineered peptide substrates as protease-specific probes. To identify tumor specific activity profiles, local sampling of the tumor microenvironment is necessary, such as through remote control of probes, which are only activated at the tumor site. Alternating magnetic fields (AMFs) provide an attractive option to remotely apply local triggering signals because they penetrate deep into the body and are not likely to interfere with biological processes due to the weak magnetic properties of tissue. Here, we report the design and evaluation of a protease-activity nanosensor that can be remotely activated at the site of disease via an AMF at 515 kHz and 15 kA/m. Our nanosensor was composed of thermosensitive liposomes containing functionalized protease substrates that were unveiled at the target site by remotely triggered heat dissipation of coencapsulated magnetic nanoparticles (MNPs). This nanosensor was combined with a unique detection assay to quantify the amount of cleaved substrates in the urine. We applied this spatiotemporally controlled system to determine tumor protease activity in vivo and identified differences in substrate cleavage profiles between two mouse models of human colorectal cancer.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Massachusetts Institute of Technology. Research Laboratory of Electronics
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1021/ACS.NANOLETT.6B02670
