Clinical translational barriers against nanoparticle-based imaging agents.

ABSTRACT

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.