Landesman-Milo Dalit, Peer Dan
Laboratory of NanoMedicine, Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University , Tel Aviv 69978, Israel.
Bioconjug Chem. 2016 Apr 20;27(4):855-62. doi: 10.1021/acs.bioconjchem.5b00607. Epub 2016 Jan 20.
The use of nanoparticles as anticancer drug carriers has been studied for over 50 years. These nanoparticles that can carry drugs are now termed "nanomedicines". Since the approval of the first FDA "nanodrug", DOXIL in 1995, tremendous efforts have been made to develop hundreds of nanomedicines based on different materials. The development of drug nanocarriers (NCs) for cancer therapy is especially challenging and requires multidisciplinary approach. Not only is the translation from a lab scale production of the NCs to clinical scale a challenge, but tumor biology and its unique physiology also possess challenges that need to be overcome with cleverer approaches. Yet, with all the efforts made to develop new strategies to deliver drugs (including small molecules and biologics) for cancer therapy, the number of new NCs that are reaching clinical trials is extremely low. Here we discuss the reasons most of the NCs loaded with anticancer drugs are not likely to reach the clinic and emphasize the importance of understanding tumor physiology and heterogeneity, the use of predictive animal models, and the importance of sharing data as key denominators for potential successful translation of NCs from a bench scale into clinical modality for cancer care.
将纳米颗粒用作抗癌药物载体的研究已经开展了50多年。这些能够携带药物的纳米颗粒如今被称为“纳米药物”。自1995年首个美国食品药品监督管理局（FDA）批准的“纳米药物”多柔比星脂质体（DOXIL）问世以来，人们付出了巨大努力，基于不同材料开发了数百种纳米药物。用于癌症治疗的药物纳米载体（NCs）的研发极具挑战性，需要多学科方法。从实验室规模生产纳米载体到临床规模的转化不仅是一项挑战，肿瘤生物学及其独特的生理学特性也带来了需要用更巧妙方法克服的挑战。然而，尽管人们为开发用于癌症治疗的药物递送新策略（包括小分子药物和生物制剂）付出了诸多努力，但进入临床试验阶段的新型纳米载体数量却极低。在此，我们讨论大多数负载抗癌药物的纳米载体不太可能进入临床应用的原因，并强调了解肿瘤生理学和异质性、使用预测性动物模型以及数据共享作为纳米载体从实验室规模成功转化为癌症治疗临床应用关键因素的重要性。
