(134a) An Optical Near Infrared Doxorubicin Sensor Discovered By Spectroscopic and Chemometric Analysis of Nanosensor Libraries

Polymer-functionalized single walled carbon nanotubes (SWNTs) are a promising new class of near-infrared (NIR) fluorescent nanomaterials with applications to non-invasive in vivo biomolecular sensing. The adsorbed polymer-phase can impart specific molecular recognition, whereby analyte binding can be monitored by measuring the resulting modulation of SWNT fluorescence. Typical preparations of polymer-functionalized SWNT nanosensors are composed of a mixture of up to fifteen nanotube chiralities, each with a unique fluorescence emission and potentially unique response to an analyte. Currently, methods for screening new nanosensor-target pairs involve searching for broad changes in fluorescence intensity and do not capture the unique fingerprint of the combined nanosensor chiralities. Herein, we demonstrate rapid and quantitative analysis of fluorescence emission spectra collected from chirality-mixed SWNT-polymer conjugate library screens with distance metric calculations, hierarchical clustering (HC) and principal component analysis (PCA). SWNT-polymer conjugates each functionalized with a different polymer corona phase, including polynucleotides, phospholipids, and amphiphilic heteropolymers, are screened against a panel of >40 biological targets. Our analysis quickly identifies nanosensor responses to difference analytes, including changes in intensity and shifts in peak wavelength, using multivariate approaches without the need for time-intensive non-linear regression fitting of individual spectral peaks. Analytes that induce similar responses, e.g. catecholamines, are grouped using hierarchical clustering, demonstrating that our approach can enable classification of nanosensor-target interactions. Our approach further identifies a novel NIR nanosensor for the detection of the chemotherapeutic doxorubicin (DOX) with µM sensitivity. We find that the kinetics of binding as well as the optical response of nanosensors to DOX is strongly dependent on the polynucleotide sequence used to functionalize the SWNT. Furthermore, we show that the fluorescence intensity increases and blue-shifted emission of the nanosensor is a combination of an interaction between the DOX and the SWNT surface as well as a perturbation to the conformation of DNA in its corona-phase. Finally, we demonstrate imaging of DOX distribution in biological tissues, and extrapolate its use to image drug bio-distributions in vivo.