Magnetically Actuated Protease Sensors for in Vivo Tumor Profiling.

Nano Lett
Authors
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.

Year of Publication
2016
Journal
Nano Lett
Volume
16
Issue
10
Pages
6303-6310
Date Published
2016 Oct 12
ISSN
1530-6992
DOI
10.1021/acs.nanolett.6b02670
PubMed ID
27622711
Links
Grant list
P30 CA014051 / CA / NCI NIH HHS / United States
P30 ES002109 / ES / NIEHS NIH HHS / United States