Center for Research at the Bio/Nano Interface, Department of Chemistry, UF Genetics Institute, University of Florida, Gainesville, Florida 32611-7200, USA.
Chemistry. 2010 Mar 22;16(12):3791-7. doi: 10.1002/chem.200901546.
Functional nanomaterials based on molecular self-assembly hold great promise for applications in biomedicine and biotechnology. However, their efficacy could be a problem and can be improved by precisely controlling the size, structure, and functions. This would require a molecular engineering design capable of producing monodispersed functional materials characterized by beneficial changes in size, shape, and chemical structure. To address this challenge, we have designed and constructed a series of amphiphilic oligonucleotide molecules. In aqueous solutions, the amphiphilic oligonucleotide molecules, consisting of a hydrophilic oligonucleotide covalently linked to hydrophobic diacyllipid tails, spontaneously self-assemble into monodispersed, three-dimensional micellar nanostructures with a lipid core and a DNA corona. These hierarchical architectures are results of intermolecular hydrophobic interactions. Experimental testing further showed that these types of micelles have excellent thermal stability and their size can be fine-tuned by changing the length of the DNA sequence. Moreover, in the micelle system, the molecular recognition properties of DNA are intact, thus, our DNA micelles can hybridize with complimentary sequences while retaining their structural integrity. Importantly, when interacting with cell membranes, the highly charged DNA micelles are able to disintegrate themselves and insert into the cell membrane, completing the process of internalization by endocytosis. Interestingly, the fluorescence was found accumulated in confined regions of cytosole. Finally, we show that the kinetics of this internalization process is size-dependent. Therefore, cell permeability, combined with small sizes and natural nontoxicity are all excellent features that make our DNA-micelles highly suitable for a variety of applications in nanobiotechnology, cell biology, and drug delivery systems.
基于分子自组装的功能纳米材料在生物医药和生物技术领域有很大的应用前景。然而，它们的疗效可能是一个问题，可以通过精确控制其大小、结构和功能来提高。这需要一种分子工程设计，能够生产出具有有益的大小、形状和化学结构变化的单分散功能材料。为了解决这个挑战，我们设计并构建了一系列两亲性寡核苷酸分子。在水溶液中，由亲水寡核苷酸共价连接疏水二酰基脂质尾巴组成的两亲性寡核苷酸分子自发自组装成具有脂质核和 DNA 冠状物的单分散、三维胶束纳米结构。这些分层结构是分子间疏水相互作用的结果。实验测试进一步表明，这些类型的胶束具有极好的热稳定性，并且通过改变 DNA 序列的长度可以精细调节其大小。此外，在胶束体系中，DNA 的分子识别特性保持完整，因此，我们的 DNA 胶束可以与互补序列杂交，同时保持其结构完整性。重要的是，当与细胞膜相互作用时，带高电荷的 DNA 胶束能够自行解体并插入细胞膜，通过内吞作用完成内化过程。有趣的是，荧光被发现积聚在细胞质的局限区域。最后，我们发现这种内化过程的动力学是尺寸依赖性的。因此，细胞通透性、小尺寸和天然的非毒性结合在一起，使得我们的 DNA 胶束非常适合在纳米生物技术、细胞生物学和药物传递系统中的各种应用。
