Colloidal Gold: A Novel Nanoparticle Vector for Tumor Directed Drug Delivery

TLDR

Colloidal gold nanoparticles have been used therapeutically and diagnostically, but their application for in vivo drug delivery has not yet been reported. This study develops a colloidal gold (cAu) nanoparticle vector to deliver tumor necrosis factor (TNF) specifically to solid tumors in mice. The vector, PT‑cAu‑TNF, is composed of thiol‑derivatized PEG and recombinant human TNF covalently attached to the gold nanoparticle surface. Intravenous PT‑cAu‑TNF rapidly accumulates in MC‑38 colon carcinoma tumors with negligible uptake in healthy organs, reduces tumor burden more effectively, and is less toxic than native TNF at lower doses.

Abstract

Colloidal gold, a sol comprised of nanoparticles of Au0, 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.