Bottini Massimo, Sacchetti Cristiano, Pietroiusti Antonio, Bellucci Stefano, Magrini Andrea, Rosato Nicola, Bottini Nunzio
J Nanosci Nanotechnol. 2014 Jan;14(1):98-114. doi: 10.1166/jnn.2014.9010.
The recent advent of nanomedicine holds potential to revolutionize cancer therapy. This innovative discipline has paved the way for the emergence of a new class of drugs based on nanoengineered particles. These "nanodrugs" are designed to greatly enhance drug therapeutic indices. First-generation nanodrugs consisted of conventional anti-cancer drugs loaded into/onto nanoengineered particles (nanocarriers) devoid of targeting features (non-targeted nanodrugs). Non-targeted nanodrugs have provided the opportunity to carry large amounts of drugs, including poorly water-soluble and/or permeable drugs, to several types of tumors, improving the therapeutic index with respect to comparable free drugs. Although effective, the primary delivery mechanism of non-targeted nanodrugs was through passive tissue accumulation, due to pathophysiological differences between tumor-associated and healthy vessels, and through non-specific targeting of cell subsets, posing the danger of off-target binding and effects. Recently, the therapeutic indices of certain anti-cancer drugs were further improved by attaching targeting ligands to nanodrugs (targeted-nanodrugs). Targeted-nanodrugs selectively bind to cognate receptors expressed on target cells and enter cells more efficiently than non-targeted formulations. Although these advancements have been sufficiently beneficial to place targeted-nanodrugs into clinical development for use in cancer therapy, they also come at a price. The addition of ligands to drug-loaded nanocarriers often leads to additional synthesis steps and costs, and more complex biological performance relative to ligand-devoid nanodrugs. Here, we will discuss the benefits and challenges facing the addition of targeting features to nanodrugs for cancer therapy.
纳米医学的最新出现有望彻底改变癌症治疗。这一创新学科为基于纳米工程颗粒的新型药物的出现铺平了道路。这些“纳米药物”旨在大幅提高药物治疗指数。第一代纳米药物由装载到缺乏靶向特性的纳米工程颗粒（纳米载体）上/内的传统抗癌药物组成（非靶向纳米药物）。非靶向纳米药物为将大量药物，包括水溶性差和/或渗透性差的药物，输送到多种类型的肿瘤提供了机会，相对于可比的游离药物提高了治疗指数。尽管有效，但非靶向纳米药物的主要递送机制是通过被动组织蓄积，这是由于肿瘤相关血管和健康血管之间的病理生理差异，以及通过细胞亚群的非特异性靶向，存在脱靶结合和效应的风险。最近，通过将靶向配体连接到纳米药物上（靶向纳米药物），某些抗癌药物的治疗指数得到了进一步提高。靶向纳米药物选择性地与靶细胞上表达的同源受体结合，并比非靶向制剂更有效地进入细胞。尽管这些进展已经足够有益，使靶向纳米药物进入癌症治疗的临床开发，但它们也有代价。在载药纳米载体上添加配体通常会导致额外的合成步骤和成本，以及相对于无配体纳米药物更复杂的生物学性能。在这里，我们将讨论在纳米药物中添加靶向特性用于癌症治疗所面临的益处和挑战。
