An in Vivo Nanosensor Measures Compartmental Doxorubicin Exposure

Abstract

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.

Binding Affinity and Conformational Preferences Influence Kinetic Stability of Short Oligonucleotides on Carbon Nanotubes

“…Single wall carbon nanotubes (SWNTs) comprise a key component of many new nanotechnology applications for sensing, biological imaging, electronics, and gene delivery, among others [1][2][3][4][5][6][7][8][9][10][11] . Noncovalent polymer adsorption is a widely used method to confer and optimize desired functionalities to SWNTs, while solubilizing them in aqueous environments.…”

Fluorescent Single-Walled Carbon Nanotubes for Protein Detection

“…This nanosensor was immobilized on a glass surface, on which human blood platelets were cultured, and were shown to detect serotonin release patterns from the cells in real time [115]. Additionally, DNA-wrapped SWCNTs were utilized for the detection of a single-stranded RNA genome of an intact HIV particle [116] and of doxorubicin, a chemotherapy drug effective against dividing cells due to its affinity to DNA [117]. Further, DNA-SWCNTs were engineered to quantify microRNA hybridization, by a solvatochromic-like response following DNA displacement from the nanotubes' surface [118].…”

A Wearable Optical Microfibrous Biomaterial with Encapsulated Nanosensors Enables Wireless Monitoring of Oxidative Stress

“…Single-walled carbon nanotubes (SWCNTs) with engineered wrappings have recently been developed and utilized in various disparate fields ranging from additives that strengthen material composites [32,33] to biomedical applications including near-infrared (NIR) optical biosensing, [34][35][36] and biological imaging. [37,38] The electronic bandgap energies of SWCNTs are dependent on their chiral identity, denoted by integers (n,m), and vary based on diameter and rollup angle, resulting in various semiconducting species that exhibit distinct narrowbandwidth photoluminescence in the second NIR window.…”