title: Designing nanoconjugates to effectively target pancreatic cancer cells in vitro and in vivo.
abstract: BACKGROUND
  Pancreatic cancer is the fourth leading cause of cancer related deaths in America. Monoclonal antibodies are a viable treatment option for inhibiting cancer growth. Tumor specific drug delivery could be achieved utilizing these monoclonal antibodies as targeting agents. This type of designer therapeutic is evolving and with the use of gold nanoparticles it is a promising approach to selectively deliver chemotherapeutics to malignant cells. Gold nanoparticles (GNPs) are showing extreme promise in current medicinal research. GNPs have been shown to non-invasively kill tumor cells by hyperthermia using radiofrequency. They have also been implemented as early detection agents due to their unique X-ray contrast properties; success was revealed with clear delineation of blood capillaries in a preclinical model by CT (computer tomography). The fundamental parameters for intelligent design of nanoconjugates are on the forefront. The goal of this study is to define the necessary design parameters to successfully target pancreatic cancer cells.
  
  
  RESULTS
  The nanoconjugates described in this study were characterized with various physico-chemical techniques. We demonstrate that the number of cetuximab molecules (targeting agent) on a GNP, the hydrodynamic size of the nanoconjugates, available reactive surface area and the ability of the nanoconjugates to sequester EGFR (epidermal growth factor receptor), all play critical roles in effectively targeting tumor cells in vitro and in vivo in an orthotopic model of pancreatic cancer.
  
  
  CONCLUSIONS
  Our results suggest the specific targeting of tumor cells depends on a number of crucial components 1) targeting agent to nanoparticle ratio 2) availability of reactive surface area on the nanoparticle 3) ability of the nanoconjugate to bind the target and 4) hydrodynamic diameter of the nanoconjugate. We believe this study will help define the design parameters for formulating better strategies for specifically targeting tumors with nanoparticle conjugates.
authors: Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, Rochester, Minnesota, United States of America.
authors: Jameel Ahmad
authors: JA
authors: Khan
authors: Rachel A
authors: RA
authors: Kudgus
authors: Annamaria
authors: A
authors: Szabolcs
authors: Shamit
authors: S
authors: Dutta
authors: Enfeng
authors: E
authors: Wang
authors: Sheng
authors: S
authors: Cao
authors: Geoffry L
authors: GL
authors: Curran
authors: Vijay
authors: V
authors: Shah
authors: Steven
authors: S
authors: Curley
authors: Debabrata
authors: D
authors: Mukhopadhyay
authors: J David
authors: JD
authors: Robertson
authors: Resham
authors: R
authors: Bhattacharya
authors: Priyabrata
authors: P
authors: Mukherjee
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D000068818:Cetuximab; D006046:Gold / Q000737:chemistry*; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D058726:Nanoconjugates / Q000737:chemistry*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D058726:Nanoconjugates; D006046:Gold; D000068818:Cetuximab