title: Nanoscale radiotherapy with hafnium oxide nanoparticles.
abstract: OBJECTIVE
  There is considerable interest in approaches that could improve the therapeutic window of radiotherapy. In this study, hafnium oxide nanoparticles were designed that concentrate in tumor cells to achieve intracellular high-energy dose deposit.
  
  
  METHODS
  Conventional methods were used, implemented in different ways, to explore interactions of these high-atomic-number nanoparticles and ionizing radiation with biological systems.
  
  
  RESULTS
  Using the Monte Carlo simulation, these nanoparticles, when exposed to high-energy photons, were shown to demonstrate an approximately ninefold radiation dose enhancement compared with water. Importantly, the nanoparticles show satisfactory dispersion and persistence within the tumor and they form clusters in the cytoplasm of cancer cells. Marked antitumor activity is demonstrated in human cancer models. Safety is similar in treated and control animals as demonstrated by a broad program of toxicology evaluation.
  
  
  CONCLUSIONS
  These findings, supported by good tolerance, provide the basis for developing this new type of nanoparticle as a promising anticancer approach in human patients.
authors.affiliation: Nanobiotix, 60 rue de Wattignies, 75012, Paris, France. laurence.maggiorella@nanobiotix.com
authors.forename: Laurence
authors.initials: L
authors.lastname: Maggiorella
authors.forename: Gilles
authors.initials: G
authors.lastname: Barouch
authors.forename: Corinne
authors.initials: C
authors.lastname: Devaux
authors.forename: Agnès
authors.initials: A
authors.lastname: Pottier
authors.forename: Eric
authors.initials: E
authors.lastname: Deutsch
authors.forename: Jean
authors.initials: J
authors.lastname: Bourhis
authors.forename: Elsa
authors.initials: E
authors.lastname: Borghi
authors.forename: Laurent
authors.initials: L
authors.lastname: Levy
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D003198:Computer Simulation; D011992:Endosomes / Q000378:metabolism / Q000473:pathology; D005260:Female; D006195:Hafnium / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D009010:Monte Carlo Method; D053758:Nanoparticles / Q000008:administration & dosage* / Q000009:adverse effects; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D010087:Oxides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011859:Radiography; D047368:Tumor Burden / Q000528:radiation effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D010087:Oxides; D011838:Radiation-Sensitizing Agents; C545179:hafnium oxide; D006195:Hafnium