Tethered Lipid Bilayer Gates: Toward Extended Retention of Hydrophilic Cargo in Porous Nanocarriers

Jixi Zhang, Diti Desai, Jessica Rosenholm

    Research output: Contribution to journalArticleScientificpeer-review

    30 Citations (Scopus)

    Abstract

    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.
    Original languageUndefined/Unknown
    Pages (from-to)2352–2360
    JournalAdvanced Functional Materials
    Volume24
    Issue number16
    DOIs
    Publication statusPublished - 2014
    MoE publication typeA1 Journal article-refereed

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