Toward Developing an Antimelanoma Topical Gel from Coordination Polymers Derived from a Nitrile-Functionalized Terpyridine Ligand and Dicarboxylic Acids

With the aim of developing a vehicle-free
drug delivery (VFDD)
system, a structural rationale has been exploited to synthesize a
series of metallogelators derived from coordination polymers constituted
with a nitrile-functionalized terpyridyl ligand (L), various dicarboxylic
acids (2-amino terephthalate (2-NH2TA), 2,6-naphthalene
dicarboxylate (2,6-NDA), and 1,4-phenylene dicarboxylate (1,4-PDA)),
and transition metal salts (Zn(NO3)2·6H2O, Co(NO3)2·6H2O, Ni(NO3)2·6H2O). The coordination polymers
(CP1-CP5), thus synthesized, were fully characterized by single-crystal
X-ray diffraction (SXRD). Metallogels (CPG1-CPG5) were obtained by
mixing stoichiometric amounts of the reactants of the coordination
polymers in DMSO/water (3:2), as revealed by their single-crystal
structures. The metallogels were characterized by dynamic rheology
and electron microscopy. Biological studies revealed that the anticancer
activity of the metallogelator CPG1 against the melanoma cell line
(B16–F10) was superior to CPG2, with CPG1 being noncytotoxic
to noncancerous cell lines (E. Derm and HEK 293) within the operating
concentration range. CPG1 also showed appreciable ability to inhibit
cell migration of B16–F10 cells in a scratch assay. Mechanistic
studies indicated the involvement of apoptosis with cell cycle arrest
in the G0/G1 phase. Side population discrimination assay showed that
CPG1 could also kill the side population (SP) cells of B16–F10a
trait known to reduce the chance of metastasis. Intriguingly, CPG1
was also successful in preventing the growth of tumor spheroids derived
from B16–F10 cells, highlighting its ability to prevent cancerous
tumor growth. Thus, the corresponding metallogel CPG1 can further
be developed as a topical gel for treating skin cancer-like scenarios
because the B16–F10 cell line is often referred to as a human
skin cancer model.