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

Abstract

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 co-

Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface

“…While it is clear that nanoparticle size and shape are key factors for uptake [15][16][17] , current targeting strategies also involve conjugation of biofunctional moieties to nanoparticles in an effort to determine the biological outcomes 1,2,9,12,[18][19][20] . In some cases this seems successful, 3 but in others less so (for example targeting moieties can hinder biological barrier penetration 8,11 ).…”

Gold nanostructures: a class of multifunctional materials for biomedical applications

“…[15][16][17] Gold colloids were studied in humans in the 1950's as radiotracers for sentinel lymph node biopsy, and a phase I clinical trial has recently been completed for gold nanosphere-based drug carriers. [16][17][18] Despite the involvement of high doses of a toxic agent (tumor necrosis factor-alpha, TNF), minimal side effects were observed from treatment with gold nanospheres. 17 Nevertheless, it is important that we continue to study the biocompatibility of these materials, as This journal is c The Royal Society of Chemistry 2011 their suitability for different applications will depend heavily on a number of factors, including the size and shape of the particles, the surface coatings, and the method of administration.…”

“…46 It is also possible to conjugate certain therapeutics directly to the surface of the nanostructures, using the stealth-like properties of PEG coatings to transport highly toxic drugs to the tumor site while minimizing side effects. 16,17 The strong optical response of gold nanostructures due to LSPR is also critical to many of their biomedical applications. 14 The different optical responses that result from this phenomenon and the corresponding applications are shown in Scheme 1.…”

“…However, when TNF is conjugated to gold nanospheres, the toxicity can be greatly reduced, allowing for significantly higher dosages of TNF to be delivered to the tumor site. 16 Fig . 7 shows some of the results from in vivo mouse studies of TNF delivery and the resulting toxicity.…”

Application of nanoparticles in cancer detection by Raman scattering based techniques

“…Advantages of AuNPs when used in SERS includes SPR, size dependent specifications, easy surface modifications, lower toxicity associated with living cells, size and shape diversity. AuNPs can easily be functionalized with antibodies and other tumor targeting biomolecules through well-established conjugation procedures [49,50]. In recent years, several groups [51, 52] have demonstrated the potential of using AuNPs based on Raman tags for SERS.…”