Research Triangle Materials Science and Engineering Center, Durham, North Carolina 27708, USA.
Nanoscale. 2017 May 11;9(18):6178-6186. doi: 10.1039/c7nr00172j.
The discovery of biomimetic polypeptides that enable the biomineralization of synthetic and biosynthetic materials has resulted in the development of hybrid materials that incorporate inorganic components for potential application in drug delivery, enzyme immobilization, and surface modification. Here, we describe an approach that uses micellar assemblies of an elastin-like polypeptide (ELP) modified with silica-promoting sequences and drug conjugates that are subsequently encapsulated within a silica matrix. Incorporation of a lysine-rich tag derived from the silaffin R5 peptide into the N-terminus of a hydrophilic ELP that self-assembles upon conjugation of hydrophobic molecules at the C-terminus results in the formation of spherical micelles with a conjugated drug embedded in the core and a corona that is decorated with the silaffin peptide. These micelles serve as the building blocks for the polycondensation of silica into uniform, hybrid polypeptide-silica nanoparticles. We demonstrate proof-of-concept examples using a model hydrophobic small molecule and doxorobucin, a small molecule chemotherapeutic, and further show pH-dependent doxorubicin release from the hybrid nanoparticles.
仿生多肽的发现使合成和生物合成材料的生物矿化成为可能，从而开发出了将无机成分结合在一起的混合材料，有望应用于药物输送、酶固定化和表面修饰。在这里，我们描述了一种方法，该方法使用带有硅促进序列的弹性蛋白样多肽（ELP）的胶束组装体和随后封装在二氧化硅基质内的药物缀合物。将源自丝氨酸 R5 肽的富含赖氨酸的标签整合到亲水性 ELP 的 N 端，该 ELP 在 C 端的疏水分子缀合后会自组装，从而形成具有嵌入核心的共轭药物的球形胶束，以及带有丝氨酸肽的冠。这些胶束可用作将二氧化硅聚缩合成均匀的、混合的多肽-二氧化硅纳米粒子的构建块。我们使用模型疏水分子和阿霉素（一种小分子化疗药物）证明了概念验证示例，并进一步显示了从混合纳米粒子中进行 pH 依赖性阿霉素释放。
