(672g) Targeting Single Wall Carbon Nanotubes to the Nucleus Using Dispersion with Nuclear Protein Fragments

Single wall carbon nanotubes (SWCNTs) are a class of nanomaterials with unique physical and optical properties that are being developed for subcellular imaging and drug delivery. SWCNTs are hydrophobic and must be functionalized to be dispersed into aqueous solution for biological use.  Covalent modification of SWCNTs allows functionalization, but chemical modifications attenuate desired material properties of the SWCNTs for applications. To maintain optical, mechanical, and electrical properties, we exploit noncovalent interactions by dispersion using surfactant proteins. However, proteins able to disperse SWCNTs require sufficient size and hydrophobicity for stable suspensions in high ionic strength biological fluids.  To target SWCNTs to the cell nucleus, we aimed to noncovalently disperse SWCNTs with a surfactant-like protein with a nuclear localization sequence. Specifically, we show that that SWCNTs can be noncovalently dispersed using a recombinant tail domain of the nuclear lamin B1 protein.  Lamin B1 tail domains (LB1-TD) share structural and size similarity to globular proteins such as bovine serum albumin (BSA) which have previously been successful in dispersing SWCNTs. Characterization with UV-Vis-NIR absorbance spectroscopy reveals that LB1-TD produce high yield, stable, dispersions of individual SWCNTs.  LB1-TD dispersed SWCNTs are internalized into the cytoplasm and nucleus of HeLa cells without acute cytotoxicity.  Using confocal Raman imaging and spectroscopy we observe increased perinuclear localization and intense regions of nuclear accumulation of LB1-TD dispersed SWCNTs compared to BSA dispersed SWCNTs.  Further, SWCNTs appear to remain isolated within the nucleus as we also observe inherent NIR fluorescence confirming SWCNT properties are maintained.  As lamins play a key role in nuclear architecture and DNA replication, the association of SWCNTs with LB1-TD in the nucleus suggests that SWCNTs may serve as useful subcelluar biomaterials for direct manipulation of nuclear mechanics and gene expression.