Torchilin Vladimir P
Department of Pharmaceutical Sciences, Northeastern University, Mugar Building, Room 312, 360 Huntington Avenue, Boston, MA 02115, USA.
Adv Drug Deliv Rev. 2006 Dec 1;58(14):1532-55. doi: 10.1016/j.addr.2006.09.009. Epub 2006 Sep 28.
Currently used pharmaceutical nanocarriers, such as liposomes, micelles, nanoemulsions, polymeric nanoparticles and many others demonstrate a broad variety of useful properties, such as longevity in the blood allowing for their accumulation in pathological areas with compromised vasculature; specific targeting to certain disease sites due to various targeting ligands attached to the surface of the nanocarriers; enhanced intracellular penetration with the help of surface-attahced cell-penetrating molecules; contrast properties due to the carrier loading with various contrast materials allowing for direct carrier visualization in vivo; stimuli-sensitivity allowing for drug release from the carriers under certain physiological conditions, and others. Some of those pharmaceutical carriers have already made their way into clinic, while others are still under preclinical development. What could be seen much more rare, however, are the pharmaceutical nanocarriers combining several from the listed abilities. Long-circulating immunoliposomes capable of prolonged residence in the blood and specific target recognition represent one of few examples of this kind. At the same time, the enginnering of multifunctional pharmaceutical nanocarriers combinig several useful preoperties in one particle can significantly enhance the efficacy of many therapeutic and diagnostic protocols. This paper considers current status and possible future directions in the emerging area of multifunctional nanocarriers with primary attention on the combination of such properties as longevity, targetability, intracellular penetration and contrast loading.
目前使用的药物纳米载体，如脂质体、胶束、纳米乳剂、聚合物纳米颗粒等，具有多种有用的特性，例如在血液中的长时间循环，使其能够在血管受损的病理区域蓄积；由于纳米载体表面连接了各种靶向配体，可特异性靶向某些疾病部位；借助表面连接的细胞穿透分子增强细胞内渗透；由于载体负载了各种造影剂而具有造影特性，从而能够在体内直接观察到载体；刺激敏感性使得药物在某些生理条件下从载体中释放出来等等。其中一些药物载体已经进入临床应用，而其他一些仍处于临床前开发阶段。然而，更为罕见的是结合了上述几种能力的药物纳米载体。能够在血液中长时间停留并进行特异性靶向识别的长循环免疫脂质体就是这类罕见的例子之一。与此同时，在一个颗粒中结合多种有用特性的多功能药物纳米载体的工程设计，可以显著提高许多治疗和诊断方案的疗效。本文探讨了多功能纳米载体这一新兴领域的现状和未来可能的发展方向，主要关注长循环、靶向性、细胞内渗透和造影剂负载等特性的结合。
