Center for Research at Bio/nano Interface, Department of Chemistry and Shands Cancer Center, University of Florida, Gainesville, Florida 32611, United States.
ACS Nano. 2011 Oct 25;5(10):7696-9. doi: 10.1021/nn2037384.
Aptamers can bind a wide range of biomedically relevant proteins with affinities and specificities that have therapeutic utility. Although aptamers are susceptible to nuclease-mediated degradation and cannot easily cross biological barriers, specific aptamer modification can feasibly solve these problems. To address these obstacles, Lau et al. developed a general strategy for generating natural packaging and transport vehicles for targeting agents, such as aptamers and their small-molecule ligands, by using virus-like particles (VLPs) assembled from the recombinant expression of the bacteriophage Qβ coat protein. Since RNA and DNA molecules are susceptible to nuclease-mediated degradation, it is important that Qβ VLPs protect their encapsulated aptamers from nuclease-mediated degradation and enhance their permeability. Moreover, if self-assembled using natural proteins, VLPs can guarantee the biocompatibility and biodegradability of modified aptamers in therapeutic applications. Therefore, this Perspective explores the outlook for such aptamer modification strategies for nanodrug preparation and delivery applications and the challenges that lie ahead.
适配体可以与具有治疗用途的亲和力和特异性结合广泛的生物医学相关蛋白质。尽管适配体容易受到核酸酶介导的降解,并且不能轻易地穿过生物屏障,但特定的适配体修饰可以有效地解决这些问题。为了解决这些障碍,Lau 等人开发了一种通用策略,用于通过使用由噬菌体 Qβ衣壳蛋白的重组表达组装的病毒样颗粒 (VLPs),为靶向剂(如适配体及其小分子配体)生成天然的包装和运输载体。由于 RNA 和 DNA 分子易受到核酸酶介导的降解,因此 Qβ VLP 保护其包裹的适配体免受核酸酶介导的降解并增强其通透性非常重要。此外,如果使用天然蛋白质自组装,VLPs 可以保证修饰后的适配体在治疗应用中的生物相容性和可生物降解性。因此,本观点探讨了这种适配体修饰策略在纳米药物制备和递送上的应用前景以及未来面临的挑战。