Cu(II)-Organic\nCoordination Polymer Networks for Persistent\nNitric Oxide Release in Tumor Therapy

Nitric oxide (NO) plays a key role in regulating the\nimmune system\nby polarizing macrophages toward the proinflammatory M1 phenotype,\nwhich is beneficial for cancer immunotherapy. We developed a Cu-organic\ncoordination polymer network to sustainably release NO from endogenous\ndonors. This robust polymer network was constructed through a dual-interaction\nprocess: complexation and cross-linking. The carboxylate groups of\ndeprotonated 4-((6-(acryloyloxy)hexyl)oxy)benzoic acid (BA) served\nas bidentate ligands for the formation of Cu(II) complexes. The acrylate\nmoiety of BA anchored these complexes in the polymer network, forming\na cross-linked film. Cu ions within the network catalytically promoted\nNO release from <i>S</i>-nitrosoglutathione, maintaining\nthis release even after 90 days in a physiological environment. The\nreleased NO effectively polarized both resting (M0) and tumor-promoting\n(M2) macrophages to the M1 phenotype. With their demonstrated physiological\nstability and sustained NO release performance, BA-Cu films hold potential\nas anticancer patches capable of continuously promoting antitumoral\nmacrophages.