Polak Roberta, Crouzier Thomas, Lim Rosanna M, Ribbeck Katharina, Beppu Marisa M, Pitombo Ronaldo N M, Cohen Robert E, Rubner Michael F
School of Pharmaceutical Sciences, University of Sao Paulo, USP , Sao Paulo, SP 05508-000, Brazil.
Biomacromolecules. 2014 Aug 11;15(8):3093-8. doi: 10.1021/bm5006905. Epub 2014 Jul 8.
The layer-by-layer (LbL) assembly of thin films on surfaces has proven to be an extremely useful technology for uses ranging from optics to biomedical applications. Releasing these films from the substrate to generate so-called free-standing multilayer films opens a new set of applications. Current approaches to generating such materials are limited because they can be cytotoxic, difficult to scale up, or have undesirable side reactions on the material. In this work, a new sacrificial thin film system capable of chemically triggered dissolution at physiological pH of 7.4 is described. The film was created through LbL assembly of bovine submaxillary mucin (BSM) and the lectin jacalin (JAC) for a (BSM/JAC) multilayer system, which remains stable over a wide pH range (pH 3-9) and at high ionic strength (up to 5 M NaCl). This stability allows for subsequent LbL assembly of additional films in a variety of conditions, which could be released from the substrate by incubation in the presence of a competitive inhibitor sugar, melibiose, which selectively disassembles the (BSM/JAC) section of the film. This novel multilayer system was then applied to generate free-standing, 7 μm diameter, circular ultrathin films, which can be attached to a cell surface as a "backpack". A critical thickness of about 100 nm for the (BSM/JAC) film was required to release the backpacks from the glass substrate, after incubation in melibiose solution at 37 °C for 1 h. Upon their release, backpacks were subsequently attached to murine monocytes without cytotoxicity, thereby demonstrating the compatibility of this mucin-based release system with living cells.
在表面上逐层（LbL）组装薄膜已被证明是一项极其有用的技术，其应用范围从光学领域到生物医学应用。将这些薄膜从基底上释放以生成所谓的独立多层膜开启了一系列新的应用。目前生成此类材料的方法存在局限性，因为它们可能具有细胞毒性、难以扩大规模，或者在材料上会产生不良的副反应。在这项工作中，描述了一种新型的牺牲薄膜系统，该系统能够在生理pH值7.4下通过化学触发溶解。该薄膜是通过牛下颌粘液素（BSM）和凝集素红豆素（JAC）的LbL组装形成的（BSM/JAC）多层系统，其在较宽的pH范围（pH 3 - 9）和高离子强度（高达5 M NaCl）下保持稳定。这种稳定性使得在各种条件下可以随后进行额外薄膜的LbL组装，通过在竞争性抑制剂糖蜜二糖存在下孵育，可以将其从基底上释放，糖蜜二糖会选择性地拆解薄膜的（BSM/JAC）部分。然后将这种新型多层系统应用于生成直径为7μm的独立圆形超薄膜，该薄膜可以作为“背包”附着在细胞表面。在37°C下于蜜二糖溶液中孵育1小时后，（BSM/JAC）薄膜需要约100nm的临界厚度才能从玻璃基底上释放出“背包”。释放后，“背包”随后附着在小鼠单核细胞上且无细胞毒性，从而证明了这种基于粘液素的释放系统与活细胞的兼容性。
