Colloidal gold: a novel nanoparticle vector for tumor directed drug delivery.
Colloidal gold, a sol comprised of nanoparticles of Au(0), has been used as a therapeutic for the treatment of cancer as well as an indicator for immunodiagnostics. However, the use of these gold nanoparticles for in vivo drug delivery has never been described. This communication outlines the development of a colloidal gold (cAu) nanoparticle vector that targets the delivery of tumor necrosis factor (TNF) to a solid tumor growing in mice. The optimal vector, designated PT-cAu-TNF, consists of molecules of thiol-derivatized PEG (PT) and recombinant human TNF that are directly bound onto the surface of the gold nanoparticles. Following intravenous administration, PT-cAu-TNF rapidly accumulates in MC-38 colon carcinoma tumors and shows little to no accumulation in the livers, spleens (i.e., the RES) or other healthy organs of the animals. The tumor accumulation was evidenced by a marked change in the color of the tumor as it acquired the bright red/purple color of the colloidal gold sol and was coincident with the active and tumor-specific sequestration of TNF. Finally, PT-cAu-TNF was less toxic and more effective in reducing tumor burden than native TNF since maximal antitumor responses were achieved at lower doses of drug.
Paciotti
Giulio F
GF
CytImmune Sciences, Inc., College Park, Maryland 20740, USA. gpaciotti@cytimmune.com
Myer
Lonnie
L
Weinreich
David
D
Goia
Dan
D
Pavel
Nicolae
N
McLaughlin
Richard E
RE
Tamarkin
Lawrence
L
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D017979:Gold Colloid / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D008863:Microspheres; D012157:Mononuclear Phagocyte System / Q000378:metabolism; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism*; D010316:Particle Size; D010984:Platinum / Q000008:administration & dosage / Q000737:chemistry; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000737:chemistry
D000970:Antineoplastic Agents; D017979:Gold Colloid; D007202:Indicators and Reagents; D014409:Tumor Necrosis Factor-alpha; D010984:Platinum