UNASSIGNED: Single-walled @entity505 nanotubes (SWCNTs) have great potential for cell-based therapies due to their unique intrinsic optical and physical characteristics. Consequently, broad classes of dispersants have been identified that individually suspend SWCNTs in water and cell media in addition to reducing nanotube @entity137 to cells. Unambiguous control and verification of the localization and distribution of SWCNTs within cells, particularly to the nucleus, is needed to advance subcellular technologies utilizing nanotubes. Here we report delivery of SWCNTs to the nucleus by noncovalently attaching the tail domain of the nuclear protein @entity44284 ( @entity44284 ), which we engineer from the full-length @entity44284 cDNA. More than half of this low molecular weight globular protein is intrinsically disordered but has an immunoglobulin-fold composed of a central hydrophobic core, which is highly suitable for associating with SWCNTs, stably suspending SWCNTs in water and cell media. In addition, @entity44284 has an exposed nuclear localization sequence to promote active nuclear import of SWCNTs. These SWCNTs- @entity44284 dispersions in water and cell media display near-infrared (NIR) absorption spectra with sharp van Hove peaks and an NIR fluorescence spectra, suggesting that @entity44284 individually disperses nanotubes. The dispersing capability of SWCNTs by @entity44284 is similar to that by albumin proteins. The SWCNTs- @entity44284 dispersions with concentrations >= 150  g/mL (>= 30  g/mL) in water (cell media) remain stable for >= 75 days (>= 3 days) at 4   C (37   C). Further, molecular dynamics modeling of association of @entity44284 with SWCNTs reveal that the exposure of the nuclear localization sequence is independent of @entity44284 binding conformation. Measurements from confocal Raman spectroscopy and microscopy, NIR fluorescence imaging of SWCNTs, and fluorescence lifetime imaging microscopy show that millions of these SWCNTs- @entity44284 complexes enter HeLa cells, localize to the nucleus of cells, and interact with DNA. We postulate that the modification of native cellular proteins as noncovalent dispersing agents to provide specific transport will open new possibilities to utilize both SWCNT and protein properties for multifunctional subcellular targeting applications. Specifically, nuclear targeting could allow delivery of anticancer therapies, genetic treatments, or DNA to the nucleus.

Delivering Single-Walled XXXX Nanotubes to the Nucleus Using Engineered Nuclear Protein Domains.

@entity505 :: ('MESH:D002244', 'Chemical') :: ['carbon'] @entity44284 :: ('4001', 'Gene') :: ['LB1', 'LMNB1', 'lamin B1'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity']
@entity505 :: (MESH:D002244,Chemical) :: ['Carbon']
