期刊
JOURNAL OF CONTROLLED RELEASE
卷 345, 期 -, 页码 512-536出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2022.03.043
关键词
EPR effect; Nanomedicine; Tumor microenvironment; Clinical trials
资金
- JSPS Overseas Research Fellowships [202060159]
- Astellas Foundation for Research on Metabolic Disorders
- Wyss Institute
- John A Paulson School of Engineering & Applied Sciences at Harvard University
This review examines the key advances in strategies to enhance the extravasation and retention effect of nanoparticles, as well as analyzes the clinical trials and translation of these strategies.
Many efforts have been made to achieve targeted delivery of anticancer drugs to enhance their efficacy and to reduce their adverse effects. These efforts include the development of nanomedicines as they can selectively penetrate through tumor blood vessels through the enhanced permeability and retention (EPR) effect. The EPR effect was first proposed by Maeda and co-workers in 1986, and since then various types of nanoparticles have been developed to take advantage of the phenomenon with regards to drug delivery. However, the EPR effect has been found to be highly variable and thus unreliable due to the complex tumor microenvironment. Various physical and pharmacological strategies have been explored to overcome this challenge. Here, we review key advances and emerging concepts of such EPR-enhancing strategies. Furthermore, we analyze 723 clinical trials of nanoparticles with EPR enhancers and discuss their clinical translation.
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