Tamoxifen-Poly(ethylene glycol)-Thiol Gold Nanoparticle Conjugates: Enhanced Potency and Selective Delivery for Breast Cancer Treatment

TitleTamoxifen-Poly(ethylene glycol)-Thiol Gold Nanoparticle Conjugates: Enhanced Potency and Selective Delivery for Breast Cancer Treatment
Publication TypeJournal Article
Year of Publication2009
AuthorsDreaden, EC, Mwakwari, SC, Sodji, QH, Oyelere, AK, EL-Sayed, MA
JournalBioconjugate Chemistry
Volume20
Pagination2247-2253
Date PublishedDec
ISBN Number1043-1802
Accession NumberWOS:000272690100006
Abstract

The breast cancer treatment drug tamoxifen has been widely administered for more than three decades. This small molecule competes with 17 beta-estradiol for binding to estrogen receptor, a hormone receptor upregulated in a majority of breast cancers, Subsequently initiating programmed cell death. We have synthesized a thiol-PEoylated tamoxifen derivative that can be used to selectively target and deliver plasmonic gold nanoparticles to estrogen receptor positive breast cancer cells with tip to 2.7-fold enhanced drug potency in vitro. Optical microscopy/spectroscopy, tirne-dependent dose-response data, and estrogen competition studies indicate that augmented activity is due to increased rates of intracellular tamoxifen transport by nanoparticle endocytosis, rather than by passive diffusion of the free drug. Both ligand- and receptor-dependent intracellular delivery of gold nanoparticles suggest that plasma membrane localized estrogen receptor alpha may facilitate selective uptake and retention of this and other therapeutic nanoparticle conjugates. Combined targeting selectivity and enhanced potency provides opportunities for both multimodal endocrine treatment strategies and adjunctive laser photothermal therapy.

DOI10.1021/bc9002212