title: Peptide modified gold nanoparticles for improved cellular uptake, nuclear transport, and intracellular retention.
abstract: Gold nanoparticles (GNPs) are being extensively used in cancer therapeutic applications due to their ability to act both as an anticancer drug carrier in chemotherapy and as a dose enhancer in radiotherapy. The therapeutic response can be further enhanced if nanoparticles (NPs) can be effectively targeted into the nucleus. Here, we present an uptake and removal of GNPs functionalized with three peptides. The first peptide (RGD peptide) enhanced the uptake, the second peptide (NLS peptide) facilitated the nuclear delivery, while the third one (pentapeptide) covered the rest of the surface and protected it from the binding of serum proteins onto the NP surface. The pentapeptide also stabilized the conjugated GNP complex. The peptide-capped GNPs showed a five-fold increase in NP uptake followed by effective nuclear localization. The fraction of NPs exocytosed was less for peptide-capped NPs as compared to citrate-capped ones. Enhanced uptake and prolonged intracellular retention of peptide-capped GNPs could allow NPs to perform their desired applications more efficiently in cells. These studies will provide guidelines for developing NPs for therapeutic applications, which will require "controlling" of the NP accumulation rate while maintaining low toxicity.
authors.affiliation: Department of Physics, Ryerson University, 350 Victoria Street, Toronto, ON M5B 2K3, Canada. devika.chithrani@ryerson.ca.
authors.forename: C
authors.initials: C
authors.lastname: Yang
authors.forename: J
authors.initials: J
authors.lastname: Uertz
authors.forename: D
authors.initials: D
authors.lastname: Yohan
authors.forename: B D
authors.initials: BD
authors.lastname: Chithrani
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002417:Cattle; D002467:Cell Nucleus / Q000378:metabolism; D019343:Citric Acid / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D005089:Exocytosis; D006046:Gold / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D036103:Nanotechnology; D022022:Nuclear Pore / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry; D013499:Surface Properties
chemical_list: D004337:Drug Carriers; D009842:Oligopeptides; D010455:Peptides; D012709:Serum Albumin; D019343:Citric Acid; D006046:Gold; C047981:arginyl-glycyl-aspartic acid