Nano Research

, Volume 11, Issue 6, pp 3453–3461 | Cite as

Enzymatic formation of curcumin in vitro and in vivo

  • Jiaqing Wang
  • Taotao Xiong
  • Jie Zhou
  • Hongjian He
  • Dongdong Wu
  • Xuewen Du
  • Xingyi Li
  • Bing Xu
Research Article


The recent classification of curcumin (Cur) as a pan-assay interference compound (PAINS) and an invalid metabolic panaceas (IMPS) candidate demonstrated the controversial nature of Cur as a drug lead owing to its aggregation in aqueous phase and inherent instability in vivo. Here, we report a simple prodrug approach to generate nanoparticles of Curin situ that allow it to function reproducibly as an anticancer and an anti-inflammatory agent. Diphosphorylated curcumin (Cur-2p), a precursor of Cur and a substrate of alkaline phosphatase (ALP), exhibited drastically improved chemical stability and low aggregation in water. After conversion to curcumin around or inside cancer cells by ALP, Cur-2p selectively inhibited cancer cells that overexpressed ALP, but did not affect normal cells. Moreover, the intravitreal injection of Cur-2p resulted in excellent intraocular biocompatibility with no apparent damage to the morphology and visual function of retina, as shown by fundus imaging, optical coherence tomography (OCT), and histological observation. A rodent model of uveitis showed that Cur-2p significantly suppressed the inflammation response compared with Cur. As a rational approach to investigate and apply PAINS and IMPS candidates, this work presents a straightforward method to maximize the potential of drug leads and ultimately fulfil the promises and potential clinical benefits of PAINS and IMPS candidates.


enzymatic formation curcumin nanoparticles drug discovery anti-cancer anti-inflammatory 



This work was partially supported by National Institutes of Health (No. R01CA142746 and R21AI130560), National Science Foundation (No. MRSEC-1420382), Zhejiang Provincial Natural Science Foundation of China (No. LR18H300002), the National Natural Science Foundation of China (No. 31671022).

Supplementary material

12274_2018_1994_MOESM1_ESM.pdf (8.9 mb)
Enzymatic formation of curcumin in vitro and in vivo


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Copyright information

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of ChemistryBrandeis UniversityWalthamUSA
  2. 2.Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye HospitalWenzhou Medical UniversityWenzhouChina

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