Yapa Asanka S, Wang Hongwang, Wendel Sebastian O, Shrestha Tej B, Kariyawasam Nilusha L, Kalubowilage Madumali, Perera Ayomi S, Pyle Marla, Basel Matthew T, Malalasekera Aruni P, Manawadu Harshi, Yu Jing, Toledo Yubisela, Ortega Raquel, Thapa Prem S, Smith Paul E, Troyer Deryl L, Bossmann Stefan H
Department of Chemistry, Kansas State University Manhattan KS 66506 USA
Department of Anatomy & Physiology, Kansas State University Manhattan KS USA
RSC Adv. 2018 Apr 30;8(29):16052-16060. doi: 10.1039/c8ra00717a. eCollection 2018 Apr 27.
The structure of novel binary nanosponges consisting of (cholesterol-(K/D) DEVDGC)-trimaleimide units possessing a trigonal maleimide linker, to which either lysine (K) or aspartic acid (D) are tethered, has been elucidated by means of TEM. A high degree of agreement between these findings and structure predictions through explicit solvent and then coarse-grained molecular dynamics (MD) simulations has been found. Based on the nanosponges' structure and dynamics, caspase-6 mediated release of the model drug 5(6)-carboxyfluorescein has been demonstrated. Furthermore, the binary (DK20) nanosponges have been found to be virtually non-toxic in cultures of neural progenitor cells. It is of a special importance for the future development of cell-based therapies that DK20 nanosponges were taken up efficiently by leucocytes (WBC) in peripheral blood within 3 h of exposure. The percentage of live cells among the WBC was not significantly decreased by the DK20 nanosponges. In contrast to stem cell or leucocyte cell cultures, which have to be matched to the patient, autologous cells are optimal for cell-mediated therapy. Therefore, the nanosponges hold great promise for effective cell-based tumor targeting.
由含有三角马来酰亚胺连接子的（胆固醇 -（K/D）DEVDGC）-三马来酰亚胺单元组成的新型二元纳米海绵的结构已通过透射电子显微镜（TEM）得以阐明，其中赖氨酸（K）或天冬氨酸（D）连接在该三角马来酰亚胺连接子上。已发现这些研究结果与通过显式溶剂然后粗粒度分子动力学（MD）模拟进行的结构预测之间高度吻合。基于纳米海绵的结构和动力学，已证明半胱天冬酶 -6介导的模型药物5（6）-羧基荧光素的释放。此外，已发现二元（DK20）纳米海绵在神经祖细胞培养物中几乎无毒。对于基于细胞的疗法的未来发展而言，特别重要的是，DK20纳米海绵在暴露后3小时内被外周血中的白细胞（WBC）有效摄取。DK20纳米海绵并未使白细胞中的活细胞百分比显著降低。与必须与患者匹配的干细胞或白细胞细胞培养物不同，自体细胞是细胞介导疗法的最佳选择。因此，纳米海绵在基于细胞的有效肿瘤靶向方面具有巨大潜力。
