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Glutathione-responsive self-delivery nanoparticles assembled by curcumin dimer for enhanced intracellular drug delivery.

Abstract：

:Poor water solubility, short half-life, and low drug efficacy posed a challenge for clinical application of curcumin (CUR). In this work, a kind of CUR prodrug was synthesized by coupling two CUR molecules with a mono-thioether linker for glutathione (GSH)-responsive drug delivery. The synthesized CUR prodrug (CUR-S-CUR dimer) could self-assemble into the homogeneous spherical nanoparticles (NPs) in aqueous solution followed by surface functionalization of trace amounts of DSPE-PEG. These CUR-S-CUR@PEG NPs exhibited a small particle size of ∼100 nm, high CUR-loading content of ∼78 wt%, and good colloid stability. Moreover, the CUR-S-CUR@PEG NPs demonstrated much more efficient cellular uptake and intracellular/nuclear drug delivery compared with free CUR, indicating the advantages of small molecular prodrug assembly. In addition, the GSH with high concentration in tumor cells could trigger the disassembly of CUR-S-CUR@PEG NPs. Furthermore, the cytotoxicity assays indicated that the CUR-S-CUR@PEG NPs exhibited the comparable inhibition effect of tumor cell proliferation with free CUR due to sustained drug release. Therefore, these stimuli-responsive CUR-S-CUR@PEG NPs might have promising potential for highly efficient intracellular drug delivery and controlled drug release in cancer therapy.

journal_name

Int J Pharm

journal_title

International journal of pharmaceutics

authors

Zhang H,Zhang Y,Chen Y,Zhang Y,Wang Y,Zhang Y,Song L,Jiang B,Su G,Li Y,Hou Z

doi

10.1016/j.ijpharm.2018.07.061

subject

Has Abstract

pub_date

2018-10-05 00:00:00

pages

230-238

issue

1-2

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(18)30536-2

journal_volume

549

pub_type

杂志文章

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