PMID- 26098461 OWN - NLM STAT- MEDLINE DCOM- 20160504 LR - 20150715 IS - 1944-8252 (Electronic) IS - 1944-8244 (Linking) VI - 7 IP - 27 DP - 2015 Jul 15 TI - Subcellular Partitioning and Analysis of Gd3+-Loaded Ultrashort Single-Walled Carbon Nanotubes. PG - 14593-602 LID - 10.1021/acsami.5b04851 [doi] AB - Magnetic resonance imaging (MRI) is of vast clinical utility, with tens of millions of scans performed annually. Chemical contrast agents (CAs) can greatly enhance the diagnostic potential of MRI, and approximately 50% of MRI scans use CAs. However, CAs have significant limitations such as low contrast enhancement, lack of specificity, and potential toxicity. Recently developed, Gd3+-loaded ultrashort single-walled carbon nanotubes, also referred to as gadonanotubes or GNTs, exhibit approximately 40 times the relaxivities of clinical CAs, representing a potential major advance in clinically relevant MRI CA materials. Although initial cytotoxicity and MRI studies have suggested great promise for GNTs, relatively little is known regarding their subcellular interactions, which are crucial for further, safe development of GNTs as CAs. In this work, we administered GNTs to a well-established human cell line (HeLa) and to murine macrophage-like cells (J774A.1). GNTs were not acutely cytotoxic and did not reduce proliferation, except for the highest exposure concentration of 27 mug/mL for J774A.1 macrophages, yet bulk uptake of GNTs occurred in minutes at picogram quantities, or millions of GNTs per cell. J774A.1 macrophages internalized substantially more GNTs than HeLa cells in a dose-dependent manner, and Raman imaging of the subcellular distribution of GNTs revealed perinuclear localization. Fluorescence intensity and lifetime imaging demonstrated that GNTs did not grossly alter subcellular compartments, including filamentous-actin structures. Together, these results provide subcellular evidence necessary to establish GNTs as a new MRI CA material. FAU - Holt, Brian D AU - Holt BD FAU - Law, Justin J AU - Law JJ AD - double daggerDepartment of Chemistry and Smalley Center for Nanoscale Science and Technology, Rice University, Houston, Texas 77251, United States. FAU - Boyer, Patrick D AU - Boyer PD FAU - Wilson, Lon J AU - Wilson LJ AD - double daggerDepartment of Chemistry and Smalley Center for Nanoscale Science and Technology, Rice University, Houston, Texas 77251, United States. FAU - Dahl, Kris Noel AU - Dahl KN FAU - Islam, Mohammad F AU - Islam MF LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20150702 PL - United States TA - ACS Appl Mater Interfaces JT - ACS applied materials & interfaces JID - 101504991 RN - 0 (Contrast Media) RN - 0 (Nanocapsules) RN - 0 (Nanotubes, Carbon) RN - AU0V1LM3JT (Gadolinium) SB - IM MH - Contrast Media/chemistry MH - Diffusion MH - Gadolinium/*chemistry MH - HeLa Cells MH - Humans MH - Magnetic Resonance Imaging/*methods MH - Materials Testing MH - Nanocapsules/*chemistry/ultrastructure MH - Nanotubes, Carbon/*chemistry/ultrastructure MH - Particle Size MH - Subcellular Fractions/*chemistry/*ultrastructure MH - Tissue Distribution OTO - NOTNLM OT - Raman spectroscopy OT - actin OT - carbon nanotubes OT - chemical contrast agent OT - gadolinium OT - gadonanotubes OT - magnetic resonance imaging EDAT- 2015/06/23 06:00 MHDA- 2016/05/05 06:00 CRDT- 2015/06/23 06:00 PHST- 2015/06/23 06:00 [entrez] PHST- 2015/06/23 06:00 [pubmed] PHST- 2016/05/05 06:00 [medline] AID - 10.1021/acsami.5b04851 [doi] PST - ppublish SO - ACS Appl Mater Interfaces. 2015 Jul 15;7(27):14593-602. doi: 10.1021/acsami.5b04851. Epub 2015 Jul 2.