title: Active targeting of mesoporous silica drug carriers enhances γ-secretase inhibitor efficacy in an in vivo model for breast cancer.
abstract: OBJECTIVE
  In this article, we use an alternative cancer model for the evaluation of nanotherapy, and assess the impact of surface functionalization and active targeting of mesoporous silica nanoparticles (MSNPs) on therapeutic efficacy in vivo.
  
  
  METHODS
  We used the chorioallantoic membrane xenograft assay to investigate the biodistribution and therapeutic efficacy of folate versus polyethyleneimine-functionalized γ-secretase inhibitor-loaded MSNPs in breast and prostate tumor models.
  
  
  RESULTS
  γ-secretase inhibitor-loaded MSNPs inhibited tumor growth in breast and prostate cancer xenografts. Folate conjugation improved the therapeutic outcome in folic acid receptor-positive breast cancer, but not in prostate cancer lacking the receptor.
  
  
  CONCLUSIONS
  The results demonstrate that therapeutic efficacy is linked to cellular uptake of MSNPs as opposed to tumor accumulation, and show that MSNP-based delivery of γ-secretase inhibitors is therapeutically effective in both breast and prostate cancer. In this article, we present a model system for a medium-to-high throughput, cost-effective, quantitative evaluation of nanoparticulate drug carriers.
authors.affiliation: Institute for Laser Technologies in Medicine & Metrology at Ulm University, Helmholtzstrasse 12, D-89081 Ulm, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Wittig
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Rosenholm
authors.forename: Eva
authors.initials: E
authors.lastname: von Haartman
authors.forename: Jarl
authors.initials: J
authors.lastname: Hemming
authors.forename: Felicitas
authors.initials: F
authors.lastname: Genze
authors.forename: Lotta
authors.initials: L
authors.lastname: Bergman
authors.forename: Thomas
authors.initials: T
authors.lastname: Simmet
authors.forename: Mika
authors.initials: M
authors.lastname: Lindén
authors.forename: Cecilia
authors.initials: C
authors.lastname: Sahlgren
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy*; D004337:Drug Carriers / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D014227:Triazines / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: C110274:2,4,6-mesitylenesulfonyl-3-nitro-1,2,4-triazolide; D004337:Drug Carriers; D004791:Enzyme Inhibitors; D014227:Triazines; D012822:Silicon Dioxide; D053829:Amyloid Precursor Protein Secretases
keywords: Notch signaling; chorioallantoic membrane; folic acid receptor; mesoporous silica nanoparticle; targeted cancer therapy