Tumor targeting with antibody-functionalized, radiolabeled carbon nanotubes.

نویسندگان

  • Michael R McDevitt
  • Debjit Chattopadhyay
  • Barry J Kappel
  • Jaspreet Singh Jaggi
  • Scott R Schiffman
  • Christophe Antczak
  • Jon T Njardarson
  • Renier Brentjens
  • David A Scheinberg
چکیده

UNLABELLED Single-walled carbon nanotubes (CNT) are mechanically robust graphene cylinders with a high aspect ratio that are comprised of sp(2)-bonded carbon atoms and possessing highly regular structures with defined periodicity. CNT exhibit unique mechanochemical properties that can be exploited for the development of novel drug delivery platforms. We hypothesized that novel prototype nanostructures consisting of biologics, radionuclides, fluorochromes, and CNT could be synthesized and designed to target tumor cells. METHODS Tumor-targeting CNT constructs were synthesized from sidewall-functionalized, water-soluble CNT platforms by covalently attaching multiple copies of tumor-specific monoclonal antibodies, radiometal-ion chelates, and fluorescent probes. The constructs were characterized spectroscopically, chromatographically, and electrophoretically. The specific reactivity of these constructs was evaluated in vitro by flow cytometry and cell-based immunoreactivity assays and in vivo using biodistribution in a murine xenograft model of lymphoma. RESULTS A soluble, reactive CNT platform was used as the starting point to build multifunctional constructs with appended antibody, metal-ion chelate, and fluorescent chromophore moieties to effect specific targeting, to carry and deliver a radiometal-ion, and to report location, respectively. These nanoconstructs were found to be specifically reactive with the human cancer cells they were designed to target in vivo in a model of disseminated human lymphoma and in vitro by flow cytometry and cell-based immunoreactivity assays versus appropriate controls. CONCLUSION The key achievement in these studies was the selective targeting of tumor in vitro and in vivo by the use of specific antibodies appended to a soluble, nanoscale CNT construct. The ability to specifically target tumor with prototype-radiolabeled or fluorescent-labeled, antibody-appended CNT constructs was encouraging and suggested further investigation of CNT as a novel delivery platform.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Photoacoustic molecular imaging with antibody-functionalized single-walled carbon nanotubes for early diagnosis of tumor.

Single-walled carbon nanotubes (SWNT) in a poly(ethylene)ghycol solution are a biocompatible transporters with strong optical absorption in the near-infrared region, in which the biological tissue is almost transparent with very low absorbance. Here, antibody-functionalized SWNTs for tumor early detection with photoacoustic molecular imaging in vivo are reported. To lay the groundwork for this ...

متن کامل

Orientation and density control of bispecific anti-HER2 antibody on functionalized carbon nanotubes for amplifying effective binding reactivity to cancer cells.

Nanomaterial bioconjugates have gained unabated interest in the field of sensing, imaging and therapy. As a conjugation process significantly affects the biological functions of proteins, it is crucial to attach them to nanomaterials with control over their orientation and the nanomaterial-to-protein ratio in order to amplify the binding efficiency of nanomaterial bioconjugates to targets. Here...

متن کامل

Synthesizing and Characterizing Functionalized Short Multiwall Carbon Nanotubes with Folate, Magnetite and Polyethylene Glycol as Multitargeted Nanocarrier of Anti-cancer Drugs

Multifunctional nanomaterials showed graet advantages in drug delivery. Folic acid (FA) binding protein, a glycosyl phosphatidyl inositol anchored cell surface receptor for folate, is overexpressed in several human tumors, whereas it is highly restricted in normal tissues. Therefore, in this study, FA, polyethylene glycol (PEG), and Fe3O4 nanoparticles multifunctionalized short multiwall carbon...

متن کامل

Antibody covalent immobilization on carbon nanotubes and assessment of antigen binding.

Controlling the covalent bonding of antibodies onto functionalized carbon nanotubes is a key step in the design and preparation of nanotube-based conjugates for targeting cancer cells. For this purpose, an anti-MUC1 antibody (Ab) is linked to both multi-walled (MWCNTs) and double-walled carbon nanotubes (DWCNTs) using different synthetic strategies. The presence of the Ab attached to the nanotu...

متن کامل

Synthesizing and Characterizing Functionalized Short Multiwall Carbon Nanotubes with Folate, Magnetite and Polyethylene Glycol as Multitargeted Nanocarrier of Anti-cancer Drugs

Multifunctional nanomaterials showed graet advantages in drug delivery. Folic acid (FA) binding protein, a glycosyl phosphatidyl inositol anchored cell surface receptor for folate, is overexpressed in several human tumors, whereas it is highly restricted in normal tissues. Therefore, in this study, FA, polyethylene glycol (PEG), and Fe3O4 nanoparticles multifunctionalized short multiwall carbon...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Journal of nuclear medicine : official publication, Society of Nuclear Medicine

دوره 48 7  شماره 

صفحات  -

تاریخ انتشار 2007