title: A reexamination of active and passive tumor targeting by using rod-shaped gold nanocrystals and covalently conjugated peptide ligands.
abstract: The targeted delivery of nanoparticles to solid tumors is one of the most important and challenging problems in cancer nanomedicine, but the detailed delivery mechanisms and design principles are still not well understood. Here we report quantitative tumor uptake studies for a class of elongated gold nanocrystals (called nanorods) that are covalently conjugated to tumor-targeting peptides. A major advantage in using gold as a "tracer" is that the accumulated gold in tumors and other organs can be quantitatively determined by elemental mass spectrometry (gold is not a natural element found in animals). Thus, colloidal gold nanorods are stabilized with a layer of polyethylene glycols (PEGs) and are conjugated to three different ligands: (i) a single-chain variable fragment (ScFv) peptide that recognizes the epidermal growth factor receptor (EGFR); (ii) an amino terminal fragment (ATF) peptide that recognizes the urokinase plasminogen activator receptor (uPAR); and (iii) a cyclic RGD peptide that recognizes the a(v)β(3) integrin receptor. Quantitative pharmacokinetic and biodistribution data show that these targeting ligands only marginally improve the total gold accumulation in xenograft tumor models in comparison with nontargeted controls, but their use could greatly alter the intracellular and extracellular nanoparticle distributions. When the gold nanorods are administered via intravenous injection, we also find that active molecular targeting of the tumor microenvironments (e.g., fibroblasts, macrophages, and vasculatures) does not significantly influence the tumor nanoparticle uptake. These results suggest that for photothermal cancer therapy, the preferred route of gold nanorod administration is intratumoral injection instead of intravenous injection.
authors.affiliation: Department of Biomedical Engineering, Emory University, 101 Woodruff Circle Suite 2007, Atlanta, Georgia 30322, United States.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Huang
authors.forename: Xianghong
authors.initials: X
authors.lastname: Peng
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Wang
authors.forename: Dong M
authors.initials: DM
authors.lastname: Shin
authors.forename: Mostafa A
authors.initials: MA
authors.lastname: El-Sayed
authors.forename: Shuming
authors.initials: S
authors.lastname: Nie
mesh_terms: D066246:ErbB Receptors / Q000378:metabolism; D006046:Gold / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D008175:Lung Neoplasms / Q000628:therapy*; D013058:Mass Spectrometry / Q000379:methods; D008422:Materials Testing; D053768:Metal Nanoparticles / Q000737:chemistry*; D050997:Nanomedicine / Q000379:methods; D036103:Nanotechnology / Q000379:methods*; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism; D013499:Surface Properties
chemical_list: D008024:Ligands; D009842:Oligopeptides; D010455:Peptides; D055293:Receptors, Urokinase Plasminogen Activator; D011092:Polyethylene Glycols; D006046:Gold; C047981:arginyl-glycyl-aspartic acid; D066246:ErbB Receptors