Active targeting of mesoporous silica drug carriers enhances γ-secretase inhibitor efficacy in an in vivo model for breast cancer.

Abstract

AIM:

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.

MATERIALS & 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.

CONCLUSION:

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: Rainer Wittig, Jessica M Rosenholm, Eva von Haartman, Jarl Hemming, Felicitas Genze, Lotta Bergman, Thomas Simmet, Mika Lindén, Cecilia Sahlgren
• Journal: Nanomedicine (London, England) (Nanomedicine (Lond)) Vol. 9 Issue 7 Pg. 971-87 (May 2014) ISSN: 1748-6963 [Electronic] England
• PMID: 23898823 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2,4,6-mesitylenesulfonyl-3-nitro-1,2,4-triazolide
• Drug Carriers
• Enzyme Inhibitors
• Triazines
• Silicon Dioxide
• Amyloid Precursor Protein Secretases

Topics

• Amyloid Precursor Protein Secretases (antagonists & inhibitors)
• Animals
• Breast Neoplasms (drug therapy)
• Drug Carriers (chemistry)
• Enzyme Inhibitors (chemistry, therapeutic use)
• Female
• Humans
• Mice
• Mice, Nude
• Nanoparticles (chemistry)
• Porosity
• Silicon Dioxide (chemistry)
• Triazines (chemistry, therapeutic use)