Ultra-Low Doses of Chirality Sorted (6,5) Carbon Nanotubes for Simultaneous Tumor Imaging and Photothermal Therapy

Abstract

Single-walled carbon nanotubes (SWCNTs) exhibit intrinsic fluorescence and strong optical absorption in the near-infrared (NIR) biological window (0.7-1.4 μm), rendering them ideal for in vivo imaging and photothermal therapy. Advances in SWCNT sorting have led to improved nanoelectronics and are promising for nanomedicine. To date, SWCNTs used in vivo consist of heterogeneous mixtures of nanotubes and only a small subset of chirality nanotubes fluoresces or heats under a NIR laser. Here, we demonstrate that separated (6,5) SWCNTs exchanged into a biocompatible surfactant, C18-PMH-mPEG, are more than 6-fold brighter in photoluminescence on the per mass basis, afford clear tumor imaging, and reach requisite photothermal tumor ablation temperatures with a >10-fold lower injected dose than as-synthesized SWCNT mixtures while exhibiting relatively low (6,5) accumulation in the reticuloendothelial system. The intravenous injection of ∼4 μg of (6,5) SWCNTs per mouse (0.254 mg/kg) for dual imaging/photothermal therapy is, by far, the lowest reported dose for nanoparticle-based in vivo therapeutics.

A Ratiometric Sensor Using Single Chirality Near‐Infrared Fluorescent Carbon Nanotubes: Application to In Vivo Monitoring

“…Additionally, single chirality SWCNT are brighter than multichirality SWCNT mixtures, reaching six times higher fl uorescence on a permass basis. [ 21 ] Despite the strong interest in the development of ratiometric optical sensors, several limitations have restricted their successful production from chirality-separated SWCNT. A main problem has been the relative diffi culty in obtaining preparative-scale quantities of single-chirality SWCNT.…”

“…Manual separation of large volumes of single chirality SWCNT in Sephacryl columns can take several days. Similarly, corona exchange by dialysis is slow and requires numerous changes of water baths over 24 to 32 h. [ 8,21 ] These methods may also have a low percent recovery of single chirality SWCNT, and are therefore not optimal for highthroughput screening of SWCNT coatings for sensor applications. However, recent developments in SWCNT separation have produced automated and scalable chromatographic SWCNT separation protocols, which have allowed routine suspensions of high purity single chirality SWCNT in SDS.…”

Photodynamic Action of Single-Walled Carbon Nanotubes

“…4 µg per mouse=0.254 mg·kg −1 ). 51) The NIR photoluminescence intensity was 6 times higher for (6,5)-SWNTs than for an unsorted mixture of SWNTs on a weight basis. More recently, in vivo vascular imaging in mice (excitation, 735-800 nm; emission, >1000 nm) was achieved through intravenous administration (0.17 µg per mouse) of (9,4)-SWNTs, which were enriched by a dextran-based gel chromatography and dispersed in water with a PEG-phospholipid (PL) conjugate (PEG-distearoylphosphatidylethanolamine).…”

“…In a later study, the same group reported that chirality-sorted (6,5)-SWNTs showed >10-times higher photothermal heat generation than the parent SWNTs with the same mass, when illuminated at 980 nm at 0.6 W·cm −2 . 51) In vivo studies were also performed with (6,5)-SWNTs on subcutaneous tumor-bearing mice. By detecting the intrinsic Raman G band of SWTNs after intravenous administration, 59) the blood circulation half-life of (6,5)-SWNTs coated with C 18 -PMH-mPEG was determined to be 23.95±1.49 h. 51) The authors also reported that the half-life of SWNTs was extendable up to 1 d with a branched PEG (7000) chain-PL conjugate.…”

“…51) In vivo studies were also performed with (6,5)-SWNTs on subcutaneous tumor-bearing mice. By detecting the intrinsic Raman G band of SWTNs after intravenous administration, 59) the blood circulation half-life of (6,5)-SWNTs coated with C 18 -PMH-mPEG was determined to be 23.95±1.49 h. 51) The authors also reported that the half-life of SWNTs was extendable up to 1 d with a branched PEG (7000) chain-PL conjugate. 59) The tumor uptake of (6,5)-SWNTs was ca.…”