Kozlovskaya Veronika, Alexander Jenolyn F, Wang Yun, Kuncewicz Thomas, Liu Xuewu, Godin Biana, Kharlampieva Eugenia
Department of Chemistry, University of Alabama at Birmingham , Birmingham, Alabama 35294, United States.
ACS Nano. 2014 Jun 24;8(6):5725-37. doi: 10.1021/nn500512x. Epub 2014 May 27.
We report on naturally inspired hydrogel capsules with pH-induced transitions from discoids to oblate ellipsoids and their interactions with cells. We integrate characteristics of erythrocytes such as discoidal shape, hollow structure, and elasticity with reversible pH-responsiveness of poly(methacrylic acid) (PMAA) to design a new type of drug delivery carrier to be potentially triggered by chemical stimuli in the tumor lesion. The capsules are fabricated from cross-linked PMAA multilayers using sacrificial discoid silicon templates. The degree of capsule shape transition is controlled by the pH-tuned volume change, which in turn is regulated by the capsule wall composition. The (PMAA)15 capsules undergo a dramatic 24-fold volume change, while a moderate 2.3-fold volume variation is observed for more rigid PMAA-(poly(N-vinylpyrrolidone) (PMAA-PVPON)5 capsules when solution pH is varied between 7.4 and 4. Despite that both types of capsules exhibit discoid-to-oblate ellipsoid transitions, a 3-fold greater swelling in radial dimensions is found for one-component systems due to a greater degree of the circular face bulging. We also show that (PMAA-PVPON)5 discoidal capsules interact differently with J774A.1 macrophages, HMVEC endothelial cells, and 4T1 breast cancer cells. The discoidal capsules show 60% lower internalization as compared to spherical capsules. Finally, hydrogel capsules demonstrate a 2-fold decrease in size upon internalization. These capsules represent a unique example of elastic hydrogel discoids capable of pH-induced drastic and reversible variations in aspect ratios. Considering the RBC-mimicking shape, their dimensions, and their capability to undergo pH-triggered intracellular responses, the hydrogel capsules demonstrate considerable potential as novel carriers in shape-regulated transport and cellular uptake.
我们报道了具有pH诱导从盘状体转变为扁椭球体特性的天然灵感水凝胶胶囊及其与细胞的相互作用。我们将红细胞的特征（如盘状形状、中空结构和弹性）与聚（甲基丙烯酸）（PMAA）的可逆pH响应性相结合，设计出一种新型药物递送载体，其可能由肿瘤病变中的化学刺激触发。这些胶囊由使用牺牲性盘状硅模板的交联PMAA多层膜制成。胶囊形状转变的程度由pH调节的体积变化控制，而pH调节的体积变化又由胶囊壁组成调节。当溶液pH在7.4和4之间变化时，（PMAA）15胶囊经历了24倍的剧烈体积变化，而对于更刚性的PMAA - 聚（N - 乙烯基吡咯烷酮）（PMAA - PVPON）5胶囊，观察到适度的2.3倍体积变化。尽管两种类型的胶囊都表现出从盘状体到扁椭球体的转变，但由于圆形面鼓起程度更大，单组分系统在径向尺寸上的膨胀大3倍。我们还表明，（PMAA - PVPON）5盘状胶囊与J774A.1巨噬细胞、HMVEC内皮细胞和4T1乳腺癌细胞的相互作用不同。与球形胶囊相比，盘状胶囊的内化率低60%。最后，水凝胶胶囊内化后尺寸减小2倍。这些胶囊代表了一种独特的弹性水凝胶盘状体实例，能够在pH诱导下长宽比发生剧烈且可逆的变化。考虑到其模仿红细胞的形状、尺寸以及进行pH触发的细胞内反应的能力，水凝胶胶囊在形状调节运输和细胞摄取方面作为新型载体具有相当大的潜力。
