Diamide Linked gamma-Cyclodextrin Dimers as Molecular-Scale Delivery Systems for the Medicinal Pigment Curcumin to Prostate Cancer Cells

作者：Harada Takaaki; Giorgio Lauren; Harris Tiffany J; Duc Truc Pham; Huy Tien Ngo; Need Eleanor F; Coventry Brendon J; Lincoln Stephen F; Easton Christopher J; Buchanan Grant; Kee Tak W^*

来源：Molecular Pharmaceutics, 2013, 10(12): 4481-4490.

DOI：10.1021/mp400309s

• anticancer
• drug delivery
• cyclodextrin
• biocompatibility
• cell proliferation

Diamide linked gamma-cyclodextrin (gamma-CD) dimers are proposed as molecular-scale delivery agents for the anticancer agent curcumin. N,N%26apos;-Bis(6(A)-deoxy-gamma-cyclodextrin-6(A)-yl)succinamide (66 gamma CD(2)su) and N,N%26apos;-bis(6(A)-deoxy-gamma-cyclodextrin-6(A)-yl)urea (66 gamma CD(2)ur) markedly suppress the degradation of curcumin by forming a strong 1:1 cooperative binding complexes. The results presented in this study describe the potential efficacy of 66 gamma CD(2)su and 66 gamma CD(2)ur for intracellular curcumin delivery to cancer cells. Cellular viability assays demonstrated a dose-dependent antiproliferative effect of curcumin in human prostate cancer (PC-3) cells that was preserved by the curcumin-66 gamma CD(2)su complex. In contrast, delivery of curcumin by 66 gamma CD(2)ur significantly delayed the antiproliferative effect. We observed similar patterns of gene regulation in PC-3 cells for curcumin complexed with either 66 gamma CD(2)su or 66 gamma CD(2)ur in comparison to curcumin alone, although curcumin delivered by either 66 gamma CD(2)su or 66 gamma CD(2)ur induces a slightly higher up-regulation of heme oxygenase-1. Highlighting their nontoxic nature, neither 66 gamma CD(2)su nor 66 gamma CD(2)ur carriers alone had any measurable effect on cell proliferation or candidate gene expression in PC-3 cells. Finally, confocal fluorescence imaging and uptake studies were used to demonstrate the intracellular delivery of curcumin by 66 gamma CD(2)su and 66 gamma CD(2)ur. Overall, these results demonstrate effective intracellular delivery and action of curcumin when complexed with 66 gamma CD(2)su and 66 gamma CD(2)ur, providing further evidence of their potential applications to deliver curcumin effectively in cancer and other treatment settings.

• 出版日期2013-12