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

作者：Wittig Rainer; Rosenholm Jessica M; von Haartman Eva; Hemming Jarl; Genze Felicitas; Bergman Lotta; Simmet Thomas; Linden Mika; Sahlgren Cecilia^*

来源：Nanomedicine, 2014, 9(7): 971-987.

DOI：10.2217/NNM.13.62

• chorioallantoic membrane
• folic acid receptor
• mesoporous silica nanoparticle
• Notch signaling
• targeted cancer therapy

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 %26 methods: We used the chorioallantoic membrane xenograft assay to investigate the biodistribution and therapeutic efficacy of folate versus polyethyleneimine-functionalized gamma-secretase inhibitor-loaded MSNPs in breast and prostate tumor models. Results: gamma-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 gamma-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.

• 出版日期2014-5