期刊
ADVANCED FUNCTIONAL MATERIALS
卷 24, 期 16, 页码 2352-2360出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201302995
关键词
drug delivery; mesoporous silica nanoparticles; hyperbranched PEI; tethered lipid bilayers
类别
资金
- Magnus Ehrnrooth Foundation
- Centre for International Mobility (CIMO) of Finland
- Academy of Finland [137101, 140193, 260599]
- Academy of Finland (AKA) [137101, 140193, 137101, 140193] Funding Source: Academy of Finland (AKA)
A high-performance molecular gating system for efficient capping and delivery of hydrophilic cargo is reported. It integrates a mesoporous silica nanoparticle core and a lipid bilayer (LB) shell by covalent tethering via a hyperbranched polyethylenimine (PEI) cushion. When using calcein as a general model for hydrophilic drug molecules, a high payload is loaded into the porous structure due to greatly enhanced concentration of amino groups on the pore walls. Surprisingly, LB non-disruptively resides on the porous surface in this system, despite the strong positive charge from PEI, originating from the covalent tethering of the inner leaflet, as well as preferential spanning over the pore openings facilitated by the stretching of PEI chains on the particle surface. An unprecedented high retention of negatively charged hydrophilic guest molecules after up to 1 week is consequently achieved, even in the presence of a membrane disrupting agent. Furthermore, a PEI-induced charge conversion at neutral pH is conferred to the particles using a zwitterionic PC lipid as the outer leaflet of LB. Interestingly, the corresponding nanocarriers are able to promote cargo escape from endosomes. Subsequent delivery of the loaded hydrophilic cargo to the cytoplasm is observed despite the tight retention under extracellular conditions.
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