(340p) Probing Interactions of Single-Walled Carbon Nanotubes at the Nano-Bio Interface

Non-covalent hybrids of single-stranded DNA and single-walled carbon nanotubes (SWCNTs) have demonstrated applications in biomedical imaging and sensing due to their enhanced biocompatibility and photostable, environmentally-responsive near-infrared (NIR) fluorescence. Significant progress has been made in developing robust biological probes based on the sensitive optical properties of SWCNTs, however biological environments introduce complex and dynamic conditions that interact with, and ultimately modulate, their intrinsic properties. These fundamental interactions within biological settings can direct whether a nanomaterial is biocompatible and robust, or cytotoxic and disruptive to biological processes. Thus, a mechanistic understanding of such interactions and their effect on cellular function is crucial to the design of nanoscale technology for biomedical purposes.

My research at the URI NanoBio Engineering Lab focuses on improving our understanding of the fundamental interactions which occur at the interface between nanomaterials and biological systems (i.e., at the nano-bio interface). Our goal is to develop multifunctional biosensors which can investigate and characterize various intracellular processes using DNA-wrapped carbon nanotubes, which are rapidly internalized by mammalian cells via active endocytosis. Through visible and NIR fluorescence imaging in addition to confocal Raman microscopy, we show that simple modification of the DNA wrapping controls the relative uptake, intracellular optical stability, and retention of DNA-SWCNTs in murine macrophages. We found that shorter DNA strands are displaced from the SWCNT within the cell, altering their physical identity and changing the fate of the internalized nanomaterial compared to more stable long DNA wrapped SWCNTs. To further probe the dynamics of intracellular processes, we developed and applied an approach where DNA-SWCNTs play a dual role - that of a nanomaterial undergoing intracellular processing, in addition to functioning as the signal transduction element reporting these events in individual cells with single organelle resolution. This approach uncovered correlations between DNA-SWCNT concentration, dielectric modulation, and irreversible aggregation within single intracellular vesicles. An immunofluorescence assay was designed to directly observe the DNA-SWCNTs in labeled endosomal vesicles, uncovering a distinct relationship between the physical state of organelle-bound DNA-SWCNTs and the dynamic luminal conditions during endosomal maturation processes. Finally, we trained a machine learning algorithm to predict endosome type using the Raman spectra of the vesicle-bound DNA-SWCNTs, enabling major components in the endocytic pathway to be simultaneously visualized using a single intracellular reporter.

Research Interests:

My research interests are centered around the development and analysis of nanoscale sensors for biomedical applications.