Orthogonal self-assembly of an organoplatinum(II) metallacycle and cucurbit[8]uril that delivers curcumin to cancer cells

• DOI: 10.1073/pnas.1803800115
• Publication Date: 2018-07-23T19:15:08Z
• Authors: Sougata Datta; Santosh K. Misra; Manik Lal Saha; Nabajit Lahiri; Janis Louie; Dipanjan Pan; Peter J. Stang
• Keywords: Metallacycle

Curcumin (Cur) is a naturally occurring anticancer drug isolated from the Curcuma longa plant. It known to exhibit properties via inhibiting STAT3 phosphorylation process. However, its poor water solubility and low bioavailability impede clinical application. Herein, we used organoplatinum(II) ← pyridyl coordination-driven self-assembly cucurbit[8]uril (CB[8])-mediated heteroternary host-guest complex formation in concert produce an effective delivery system that transports Cur into cancer cells. Specifically, hexagon 1, containing hydrophilic methyl viologen (MV) units 3,4,5-Tris[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]benzoyl groups alternatively at vertices, has been synthesized characterized by several spectroscopic techniques. The MV of 1 underwent noncovalent complexation with CB[8] yield 4. can be encapsulated 4, 1:1:1 formation, resulting water-soluble 5. 5 exhibited ca 100-fold improved IC50 values relative free against human melanoma (C32), rodents (B16F10), hormone-responsive (MCF-7) triple-negative (MDA-MB231) breast Moreover, strong synergisms 4 combinatorial indexes <1 across all cell lines were observed. An induced apoptosis fragmented DNA pattern inhibited expression phosphor-STAT3 supported therapeutic potential