Preclinical measurements
of drug exposure to specific organs and tissues is normally performed
by destructive methods. Tissue-specific measurements are important,
especially for drugs with intractable dose-limiting toxicities, such
as doxorubicin-mediated cardiotoxicity. We developed a method to rapidly
quantify doxorubicin exposure to tissues within living organisms using
an implantable optical nanosensor that can be interrogated noninvasively
following surgical implantation. The near-infrared fluorescence of
single-walled carbon nanotubes functionalized with DNA was found to
respond to doxorubicin via a large and uniform red-shift. We found
this to be common to DNA-intercalating agents, including anthracycline
compounds such as doxorubicin. Doxorubicin was measured in buffer
and serum, intracellularly, and from single nanotubes on a surface.
Doxorubicin adsorption to the DNA-suspended nanotubes did not displace
DNA but bound irreversibly. We incorporated the nanosensors into an
implantable membrane which allowed cumulative detection of doxorubicin
exposure in vivo. On implanting the devices into
different compartments, such as subcutaneously and within the peritoneal
cavity, we achieved real-time, minimally invasive detection of doxorubicin
injected into the peritoneal cavity, as well as compartment-specific
measurements. We measured doxorubicin translocation across the peritoneal
membrane in vivo. Robust, minimally invasive pharmacokinetic
measurements in vivo suggest the suitability of this
technology for preclinical drug discovery applications.