title: Integrin αvβ3-targeted gold nanoshells augment tumor vasculature-specific imaging and therapy.
abstract: OBJECTIVE
  Gold nanoshells (NSs) have already shown great promise as photothermal actuators for cancer therapy. Integrin αvβ3 is a marker that is specifically and preferentially overexpressed on multiple tumor types and on angiogenic tumor neovasculature. Active targeting of NSs to integrin αvβ3 offers the potential to increase accumulation preferentially in tumors and thereby enhance therapy efficacy.
  
  
  METHODS
  Enzyme-linked immunosorbent assay (ELISA) and cell binding assay were used to study the in vitro binding affinities of the targeted nanoconjugate NS-RGDfK. In vivo biodistribution and tumor specificity were analyzed using 64Cu-radiolabeled untargeted and targeted NSs in live nude rats bearing head and neck squamous cell carcinoma (HNSCC) xenografts. The potential thermal therapy applications of NS-RGDfK were evaluated by subablative thermal therapy of tumor xenografts using untargeted and targeted NSs.
  
  
  RESULTS
  ELISA and cell binding assay confirmed the binding affinity of NS-RGDfK to integrin αvβ3. Positron emission tomography/computed tomography imaging suggested that tumor targeting is improved by conjugation of NSs to cyclo(RGDfK) and peaks at ~20 hours postinjection. In the subablative thermal therapy study, greater biological effectiveness of targeted NSs was implied by the greater degree of tumor necrosis.
  
  
  CONCLUSIONS
  The results presented in this paper set the stage for the advancement of integrin αvβ3-targeted NSs as therapeutic nanoconstructs for effective cancer therapy.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77030, USA.
authors.forename: Huan
authors.initials: H
authors.lastname: Xie
authors.forename: Parmeswaran
authors.initials: P
authors.lastname: Diagaradjane
authors.forename: Amit A
authors.initials: AA
authors.lastname: Deorukhkar
authors.forename: Beth
authors.initials: B
authors.lastname: Goins
authors.forename: Ande
authors.initials: A
authors.lastname: Bao
authors.forename: William T
authors.initials: WT
authors.lastname: Phillips
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Jon
authors.initials: J
authors.lastname: Schwartz
authors.forename: Sunil
authors.initials: S
authors.lastname: Krishnan
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D003301:Copper Radioisotopes; D004797:Enzyme-Linked Immunosorbent Assay; D006046:Gold / Q000737:chemistry; D006358:Hot Temperature; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D053685:Laser Therapy; D051379:Mice; D008819:Mice, Nude; D023421:Models, Animal; D058726:Nanoconjugates / Q000737:chemistry*; D057145:Nanoshells / Q000737:chemistry; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats; D011923:Rats, Nude; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods; D014183:Transplantation, Heterologous
chemical_list: D003301:Copper Radioisotopes; D039302:Integrin alphaVbeta3; D058726:Nanoconjugates; D010456:Peptides, Cyclic; C099250:cyclic (arginyl-glycyl-aspartyl-phenylalanyl-lysyl); D006046:Gold