期刊
ADVANCED FUNCTIONAL MATERIALS
卷 24, 期 44, 页码 6999-7006出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201402339
关键词
mesoporous silica nanoparticles; tumour-targeted; and logic gate; bio-responsive; drug delivery
类别
资金
- Australian Research Council [DP110902183]
- National Health and Medical Research Council [APP1024723]
- University of New South Wales
Despite the rapid development of drug delivery vehicles that react to a specific biological environment, the complexity of triggering drug release in a particular target area remains an enduring challenge. Here, the engineering of bioresponsive polymer-mesoporous silica nanoparticles (MSNs) with function akin to an AND logic gate is described. Polycaprolactone (esterase degradable) is immobilized into the core of MSNs while polyacrylic acid (PAA), which is pH responsive, covered the outside of the MSNs to create a PAA-PCL-MSNs construct. Fluorescence spectroscopy indicates that the construct releases the payload (doxorubicin, cancer drugs) in the presence of, and only in the presence of, both low pH AND esterase. Confocal microscopy and fluorescence lifetime microscopy (FLIM) demonstrate uptake of the intact construct and subsequent intracellular doxorubicin (DOX) delivery into the nucleus. Further in vitro IC50 studies demonstrate the AND logic gate delivery system results in more than an eightfold efficacy against neuroblastoma (SK-N-BE(2)) cells in comparison with normal fibroblasts (MRC-5). These results demonstrate the utility of MSN-polymer construct to create an AND gate capable of selectively delivering a drug payload.
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