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Enzymatic formation of curcumin in vitro and in vivo

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Abstract

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.

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Acknowledgements

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).

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Authors and Affiliations

  1. Department of Chemistry, Brandeis University, 415 South Street, Waltham, MA, 02454, USA

    Jiaqing Wang, Jie Zhou, Hongjian He, Dongdong Wu, Xuewen Du & Bing Xu

  2. Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou, 325027, China

    Taotao Xiong & Xingyi Li

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  1. Jiaqing Wang
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  2. Taotao Xiong
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  3. Jie Zhou
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  4. Hongjian He
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  5. Dongdong Wu
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  7. Xingyi Li
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  8. Bing Xu
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Correspondence to Xingyi Li or Bing Xu.

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Wang, J., Xiong, T., Zhou, J. et al. Enzymatic formation of curcumin in vitro and in vivo. Nano Res. 11, 3453–3461 (2018). https://doi.org/10.1007/s12274-018-1994-z

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