A1 Refereed original research article in a scientific journal
Active targeting of mesoporous silica drug carriers enhances gamma-secretase inhibitor efficacy in an in vivo model for breast cancer
Authors: Wittig R, Rosenholm JM, von Haartman E, Hemming J, Genze F, Bergman L, Simmet T, Linden M, Sahlgren C
Publisher: FUTURE MEDICINE LTD
Publication year: 2014
Journal: Nanomedicine
Journal name in source: NANOMEDICINE
Journal acronym: NANOMEDICINE-UK
Volume: 9
Issue: 7
First page : 971
Last page: 987
Number of pages: 17
ISSN: 1743-5889
eISSN: 1748-6963
DOI: https://doi.org/10.2217/NNM.13.62
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 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.
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.
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