Colloidal gold: A novel nanoparticle vector for tumor directed drug delivery

被引:891
作者
Paciotti, GF
Myer, L
Weinreich, D
Goia, D
Pavel, N
McLaughlin, RE
Tamarkin, L
机构
[1] CytImmune Sci Inc, College Pk, MD 20740 USA
[2] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA
[3] OMG dmc2 LP, S Plainfield, NJ USA
[4] Ferro Corp, S Plainfield, NJ USA
关键词
colloidal gold; drug delivery; tumor necrosis factor;
D O I
10.1080/10717540490433895
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:169 / 183
页数:15
相关论文
共 43 条
  • [1] Isolated hepatic perfusion with tumor necrosis factor and melphalan for unresectable cancers confined to the liver
    Alexander, HR
    Bartlett, DL
    Libutti, SK
    Fraker, DL
    Moser, T
    Rosenberg, SA
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 1998, 16 (04) : 1479 - 1489
  • [2] Control of tumour vascular permeability
    Baban, DF
    Seymour, LW
    [J]. ADVANCED DRUG DELIVERY REVIEWS, 1998, 34 (01) : 109 - 119
  • [3] BERGQVIST L, 1987, J NUCL MED, V28, P1424
  • [4] BRADFIELD JWB, 1980, BRIT J EXP PATHOL, V61, P617
  • [5] CHANDLER J, 2001, IVD TECHNOL, V72, P34
  • [6] Cleland J L, 1997, Pharm Biotechnol, V10, P1
  • [7] CREAVEN PJ, 1987, CANCER CHEMOTH PHARM, V20, P137
  • [8] FARADAY M., 1857, PHILOS T ROY SOC LON, V147, P145, DOI [DOI 10.1098/RSTL.1857.0011, 10.1098/rstl.1857.0011]
  • [9] Treatment of patients with melanoma of the extremity using hyperthermic isolated limb perfusion with melphalan, tumor necrosis factor, and interferon gamma: Results of a tumor necrosis factor dose-escalation study
    Fraker, DL
    Alexander, HR
    Andrich, M
    Rosenberg, SA
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 1996, 14 (02) : 479 - 489
  • [10] CONTROLLED NUCLEATION FOR REGULATION OF PARTICLE-SIZE IN MONODISPERSE GOLD SUSPENSIONS
    FRENS, G
    [J]. NATURE-PHYSICAL SCIENCE, 1973, 241 (105): : 20 - 22