Gold Nanorods Conjugated with Doxorubicin and cRGD for Combined Anticancer Drug Delivery and PET Imaging

Abstract

A multifunctional gold nanorod (GNR)-based nanoplatform for targeted anticancer drug delivery and positron emission tomography (PET) imaging of tumors was developed and characterized. An anti-cancer drug (i.e., doxorubicin (DOX)) was covalently conjugated onto PEGylated (PEG: polyethylene glycol) GNR nanocarriers via a hydrazone bond to achieve pH-sensitive controlled drug release. Tumor-targeting ligands (i.e., the cyclo(Arg-Gly-Asp-D-Phe-Cys) peptides, cRGD) and 64Cu-chelators (i.e., 1,4,7-triazacyclononane-N, N', N''-triacetic acid (NOTA)) were conjugated onto the distal ends of the PEG arms to achieve active tumor-targeting and PET imaging, respectively. Based on flow cytometry analysis, cRGD-conjugated nanocarriers (i.e., GNR-DOX-cRGD) exhibited a higher cellular uptake and cytotoxicity than non-targeted ones (i.e., GNR-DOX) in vitro. However, GNR-DOX-cRGD and GNR-DOX nanocarriers had similar in vivo biodistribution according to in vivo PET imaging and biodistribution studies. Due to the unique optical properties of GNRs, this multifunctional GNR-based nanoplatform can potentially be optimized for combined cancer therapies (chemotherapy and photothermal therapy) and multimodality imaging (PET, optical, X-ray computed tomography (CT), etc.).

Translational radionanomedicine: a clinical perspective

“…Recently developed nanocarriers could selectively release drugs or be activated in accordance with external environments for effective treatment. Such system using a gold nanorod as a multifunctional platform could be labeled with PET agents to realize a combination of chemotherapy, photothermal therapy and PET imaging (38).…”

Nanoparticles for hyperthermic therapy: synthesis strategies and applications in glioblastoma

“…More recently, Xiao et al studied GNRs conjugated with doxorubicin and cyclo(Arg-Gly-Asp-D-Phe-Cys) peptide for drug delivery in GBM. 103 Doxorubicin was covalently conjugated to PEGylated GNRs via a hydrazone bond. Flow cytometric analysis revealed that GNRs conjugated with doxorubicin and cyclo(Arg-Gly-Asp-D-Phe-Cys) peptide exhibited a higher cellular uptake and cytotoxicity than nontargeted GNRs conjugated with doxorubicin in human GBM cells.…”

pH-sensitive Au–BSA–DOX–FA nanocomposites for combined CT imaging and targeted drug delivery

“…Xiao et al 8 reported cyclic arginine-glycine-aspartic acid (cRGD) peptide-conjugated gold nanorods (GNRs) for targeted anticancer drug delivery and imaging of tumors. As one of the targeting agents, cRGD peptide actually reduced the tumor accumulation of the GNRs two-to threefold, which may reduce antitumor efficiency.…”

“…Among well-known nanomaterials, gold nanoparticles (GNPs) have gained considerable attention owing to their excellent biocompatibility, 2 inert reactivity, good photostability, facile synthesis, non-cytotoxicity 3 and solubility. 2,4 To date, GNPs have been widely studied in various biomedical applications, including bioimaging, single molecule tracking, biosensing, drug delivery [5][6][7][8][9] and as contrast-enhancing agents in X-ray and computed tomography (CT) applications. [10][11][12][13][14] Cancer is considered to be a worldwide mortal disease, which has become a major public concern.…”