Yapa Asanka S, Shrestha Tej B, Wendel Sebastian O, Kalubowilage Madumali, Yu Jing, Wang Hongwang, Pyle Marla, Basel Matthew T, Toledo Yubisela, Ortega Raquel, Malalasekera Aruni P, Thapa Prem S, Troyer Deryl L, Bossmann Stefan H
Department of Chemistry, Kansas State University, Manhattan, Kansas 66506, United States.
Department of Anatomy & Physiology, Kansas State University, Manhattan, Kansas 66506, United States.
ACS Appl Bio Mater. 2019 Jan 22;2(1):49-60. doi: 10.1021/acsabm.8b00305. Epub 2018 Dec 26.
Peptide nanosponges of low polydispersity are spontaneously formed from trigonal supramolecular building blocks in aqueous buffers, which feature cationic and/or anionic oligopeptides ( = 5-20) and a hydrophobic unit. In contrast to classical liposomes/vesicles, nanosponges feature interwoven hydrophilic and hydrophobic nanodomains and are readily taken up by mammalian cells. Perillyl alcohol is known to be a simple, but effective small molecule drug against glioma multiforme. However, its efficacy is limited by a poor bioavailability. In order to make perillyl alcohol bioavailable, two nanosponges consisting of 10 aspartates, to which perillyl alcohol is attached by means of an ester bond, and 20 lysines or arginines (type (D-POH)K and (D-POH)R) were synthesized, purified, and characterized by dynamic light scattering (DLS) and atomic force microscopy (AFM). These nanosponges were then tested in cell cultures of murine glioma cells (GL26) and murine neural progenitor cells (NPC) because the latter was previously utilized in cell-based cancer therapy. The two nanosponges exhibited significantly different biophysical properties (size distribution and ζ potentials). Consequently, different efficacies in killing GL26 and NPC were observed in serum-containing culture media. The results from these experiments confirmed that the type (D-POH)K nanosponge is a promising candidate for the (cell-mediated) cytotherapy of glioblastoma.
低多分散性的肽纳米海绵是由三角超分子构建块在水性缓冲液中自发形成的，其特征在于阳离子和/或阴离子寡肽（= 5 - 20）以及一个疏水单元。与传统的脂质体/囊泡不同，纳米海绵具有交织的亲水和疏水纳米域，并且很容易被哺乳动物细胞摄取。紫苏醇已知是一种针对多形性胶质母细胞瘤的简单但有效的小分子药物。然而，其疗效受到生物利用度差的限制。为了提高紫苏醇的生物利用度，合成、纯化了两种由10个天冬氨酸组成的纳米海绵，紫苏醇通过酯键与之相连，以及20个赖氨酸或精氨酸（(D - POH)K型和(D - POH)R型），并通过动态光散射（DLS）和原子力显微镜（AFM）进行了表征。然后在小鼠胶质瘤细胞（GL26）和小鼠神经祖细胞（NPC）的细胞培养物中测试了这些纳米海绵，因为后者先前已用于基于细胞的癌症治疗。这两种纳米海绵表现出显著不同的生物物理性质（尺寸分布和ζ电位）。因此，在含血清的培养基中观察到对GL26和NPC的杀伤效果不同。这些实验结果证实，(D - POH)K型纳米海绵是胶质母细胞瘤（细胞介导）细胞治疗的一个有前景的候选者。
