Author + information
- Feng Tian, MD,
- Ya-ting Wang, MD,
- Xiao Du, MD,
- Shi-lan Zhang, MD and
- Ling Liu, MD, PhD∗ ()
- ↵∗The Second Xiangya Hospital, Central South University, #139 Middle Renmin Road, Changsha, Hunan 410011, PR China
We read with great interest the recent paper by Cheng et al. (1) wherein they develop a nanotherapy that can target aneurysms and release drug molecules in response to the inflammatory microenvironment. The authors suggested that the nanotherapy could inhibit calcification and attenuated reactive oxygen species–mediated oxidative stress and apoptosis in cells, and the intravenously injected reactive oxygen species–responsive nanotherapy decorated with or without a peptide ligand cRGDfK and macrophage cell membrane effectively prevented aneurysm expansion in abdominal aortic aneurysm rats. It provided new insights into potential functions and conversion value of the multifunctional nanotherapy in treating aneurysms. However, there are 3 issues in the paper that should be considered.
Firstly, targeted molecular therapies could still miss targets to a certain extent; as this study’s results showed, the highest rapamycin release ratio is about 96% from reactive oxygen species–responsive rapamycin nanotherapy found at 72 h (1). Although short-term administration during the trial showed a good safety profile, long-term accumulation in the human body may result in adverse reactions of other organs because the off-target effects might increase gradually. The persistence of efficient targeting capability should be supported by experimental evidence.
Secondly, in previous reports, gelatin zymography was commonly used to analyze matrix metalloproteinases (MMPs) associated with aortic aneurysm (2), not Western blot. In addition, it is well known that active MMPs play a major role in aortic aneurysms, but the levels of latent MMPs should also be tested in the study. The levels of secreted MMPs in rat plasma should also be tested if necessary.
Thirdly, the pathogenesis of different abdominal aortic aneurysm models is different (3); the same treatment may have different effects. As mentioned by the authors in the study limitations, this nanotherapy approach really needs to be tested in other animal models.
In conclusion, more animal experiments, more rigorous experimental design, and more rational clinical researches are needed. There is still a long way to go before a groundbreaking treatment is successfully applied to humans.
Please note: This research was supported by grants from the National Natural Science Foundation of China (No. 81470577). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2019 American College of Cardiology Foundation