Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 132, Issue 36, Pages 12690-12697Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja104501a
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Funding
- US Public Health Service [RO1 CA 133697, RC2 ES018766]
- Bill & Melinda Gates Foundation through the Grand Challenges Exploration Initiative [53292]
- US DOD [DTRA 1-08-1-0041]
- National Science Foundation [CHE 0809384]
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Mesoporous silica nanoparticles (MSNP) have proven to be an extremely effective solid support for controlled drug delivery on account of the fact that their surfaces can be easily functionalized in order to control the nanopore openings. We have described recently a series of mechanized silica nanoparticles, which, under abiotic conditions, are capable of delivering cargo molecules employing a series of nanovalves. The key question for these systems has now become whether they can be adapted for biological use through controlled nanovalve opening in cells. Herein, we report a novel MSNP delivery system capable of drug delivery based on the function of beta-cyclodextrin (beta-CD) nanovalves that are responsive to the endosomal acidification conditions in human differentiated myeloid (THP-1) and squamous carcinoma (KB-31) cell lines. Furthermore, we demonstrate how to optimize the surface functionalization of the MSNP so as to provide a platform for the effective and rapid doxorubicin release to the nuclei of KB-31 cells.
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