Design and Synthesis of ZnII-Coordination Polymers Anchored with NSAIDs: Metallovesicle Formation and Multi-drug Delivery

A series of coordination polymers synthesized from a bis-pyridyl linker, namely 4,4 '-azopyridine (L), selected non-steroidal-anti-inflammatory drugs (NSAIDs), namely diclofenac (Dic), ibuprofen (Ibu), flurbiprofen (Flu), mefenamic acid (Mefe), and naproxen (Nap), and Zn(NO3)(2) were characterized by single crystal X-ray diffraction. One of the coordination polymers, namely CP3 derived from Flu, was able to form metallovesicles in DMSO, DMSO/H2O and DMSO/DMEM (biological media) as revealed by TEM, AFM and DLS. Metallovesicle formation by CP3 was further supported by loading a fluorescent dye, namely calcein, as well as an anti-cancer drug, doxorubicin hydrochloride (DOX), as revealed by UV-vis and emission spectra, and fluorescence microscopy. DOX-loaded metallovesicles of CP3 (DOX@CP3-vesicle) could be delivered in vitro to a highly aggressive human breast cancer cell line, namely MDA-MB-231, as revealed by MTT and cell migration assays, and also cell imaging performed under laser scanning confocal microscope (LSCM). Thus, a proof of concept for developing a multi-drug delivery system derived from a metallovesicle for delivering an anti-cancer drug to cancer cells is demonstrated for the first time.