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

: Wittig R, Rosenholm JM, von Haartman E, Hemming J, Genze F, Bergman L, Simmet T, Linden M, Sahlgren C

Publisher: FUTURE MEDICINE LTD

: 2014

: Nanomedicine

: NANOMEDICINE

: NANOMEDICINE-UK

: 9

: 7

: 971

: 987

: 17

: 1743-5889

: 1748-6963

DOI: https://doi.org/10.2217/NNM.13.62

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 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.