National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China; Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China.
Adv Drug Deliv Rev. 2022 Dec;191:114587. doi: 10.1016/j.addr.2022.114587. Epub 2022 Oct 26.
Nanoparticle based imaging agents (NIAs) have been intensively explored in bench studies. Unfortunately, only a few cases have made their ways to clinical translation. In this review, clinical trials of NIAs were investigated for understanding possible barriers behind that. First, the complexity of multifunctional NIAs is considered a main barrier because it brings uncertainty to batch-to-batch fabrication, and results in sophisticated in vivo behaviors. Second, inadequate biosafety studies slow down the translational work. Third, NIA uptake at disease sites is highly heterogeneous, and often exhibits poor targeting efficiency. Focusing on the aforementioned problems, key design parameters were analyzed including NIAs' size, composition, surface characteristics, dosage, administration route, toxicity, whole-body distribution and clearance in clinical trials. Possible strategies were suggested to overcome these barriers. Besides, regulatory guidelines as well as scale-up and reproducibility during manufacturing process were covered as they are also key factors to consider during clinical translation of NIAs.
基于纳米颗粒的成像剂（NIAs）在基础研究中得到了广泛的探索。不幸的是，只有少数案例成功转化为临床应用。在本综述中，我们研究了 NIAs 的临床试验，以了解其背后可能存在的障碍。首先，多功能 NIAs 的复杂性被认为是一个主要障碍，因为它给批间制造带来了不确定性，并导致了复杂的体内行为。其次，生物安全性研究的不足减缓了转化工作的进程。第三，疾病部位的 NIA 摄取具有高度异质性，并且通常表现出较差的靶向效率。针对上述问题，对临床试验中 NIAs 的大小、组成、表面特性、剂量、给药途径、毒性、全身分布和清除等关键设计参数进行了分析。提出了一些可能的策略来克服这些障碍。此外，还涵盖了监管指南以及制造过程中的规模化和可重复性，因为它们也是 NIAs 临床转化过程中需要考虑的关键因素。
