title: Enhancement of radiation effect on cancer cells by gold-pHLIP.
abstract: Previous research has shown that gold nanoparticles can increase the effectiveness of radiation on cancer cells. Improved radiation effectiveness would allow lower radiation doses given to patients, reducing adverse effects; alternatively, it would provide more cancer killing at current radiation doses. Damage from radiation and gold nanoparticles depends in part on the Auger effect, which is very localized; thus, it is important to place the gold nanoparticles on or in the cancer cells. In this work, we use the pH-sensitive, tumor-targeting agent, pH Low-Insertion Peptide (pHLIP), to tether 1.4-nm gold nanoparticles to cancer cells. We find that the conjugation of pHLIP to gold nanoparticles increases gold uptake in cells compared with gold nanoparticles without pHLIP, with the nanoparticles distributed mostly on the cellular membranes. We further find that gold nanoparticles conjugated to pHLIP produce a statistically significant decrease in cell survival with radiation compared with cells without gold nanoparticles and cells with gold alone. In the context of our previous findings demonstrating efficient pHLIP-mediated delivery of gold nanoparticles to tumors, the obtained results serve as a foundation for further preclinical evaluation of dose enhancement.
authors: Institute for Brain and Neural Systems and Department of Physics, Brown University, Providence, RI 02912;
authors: Michael P
authors: MP
authors: Antosh
authors: Physics Department, University of Rhode Island, Kingston, RI 02881;
authors: Dayanjali D
authors: DD
authors: Wijesinghe
authors: Physics Department, University of Rhode Island, Kingston, RI 02881;
authors: Samana
authors: S
authors: Shrestha
authors: Department of Physics, Brown University, Providence, RI 02912;
authors: Robert
authors: R
authors: Lanou
authors: Department of Physics, Brown University, Providence, RI 02912;
authors: Yun Hu
authors: YH
authors: Huang
authors: Institute for Brain and Neural Systems and.
authors: Thomas
authors: T
authors: Hasselbacher
authors: Institute for Brain and Neural Systems and.
authors: David
authors: D
authors: Fox
authors: Institute for Brain and Neural Systems and Department of Molecular Biology, Cell Biology and Biochemistry and.
authors: Nicola
authors: N
authors: Neretti
authors: Department of Chemistry, Brown University, Providence, RI 02912; and.
authors: Shouheng
authors: S
authors: Sun
authors: Department of Computer Science and Statistics, University of Rhode Island, Kingston, RI 02881.
authors: Natallia
authors: N
authors: Katenka
authors: Institute for Brain and Neural Systems and Department of Physics, Brown University, Providence, RI 02912; reshetnyak@mail.uri.edu Leon_Cooper@brown.edu.
authors: Leon N
authors: LN
authors: Cooper
authors: Physics Department, University of Rhode Island, Kingston, RI 02881;
authors: Oleg A
authors: OA
authors: Andreev
authors: Physics Department, University of Rhode Island, Kingston, RI 02881; reshetnyak@mail.uri.edu Leon_Cooper@brown.edu.
authors: Yana K
authors: YK
authors: Reshetnyak
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays; D006046:Gold / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000494:pharmacology; D053768:Metal Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy
chemical_list: D008565:Membrane Proteins; C533201:pHLIP protein; D006046:Gold
keywords: acidity; gold nanoparticles; radiation; targeting; tumor