Abstract
Metal-organic frameworks (MOFs) have demonstrated promise in biomedical applications as vehicles for drug delivery, as well as for the ability of copper-based MOFs to generate nitric oxide (NO) from endogenous S-nitrosothiols (RSNOs). Because NO is a participant in biological processes where it exhibits anti-inflammatory, antibacterial, and antiplatelet activation properties, it has received significant attention for therapeutic purposes. Previous work has shown that the water-stable MOF H3[(Cu4Cl)3-(BTTri)8] (H3BTTri = 1,3,5-tris(1H-1,2,3-triazol-5-yl)benzene), or CuBTTri, produces NO from RSNOs and can be included within a polymeric matrix to form NO-generating materials. While such materials demonstrate potential, the possibility of MOF degradation leading to copper-related toxicity is a concern that must be addressed prior to adapting these materials for biomedical applications. Herein, we present the first cytotoxicity evaluation of an NO-generating CuBTTri/polymer composite material using 3T3-J2 murine embryonic fibroblasts and primary human hepatocytes (PHHs). CuBTTri/polymer films were prepared from plasticized poly(vinyl chloride) (PVC) and characterized via PXRD, ATR-FTIR, and SEM-EDX. Additionally, the ability of the CuBTTri/polymer films to enhance NO generation from S-nitroso-N-acetylpenicillamine (SNAP) was evaluated. Enhanced NO generation in the presence of the CuBTTri/polymer films was observed, with an average NO flux (0.90 ± 0.13 nmol cm(-2) min(-1)) within the range associated with antithrombogenic surfaces. The CuBTTri/polymer films were analyzed for stability in phosphate buffered saline (PBS) and cell culture media under physiological conditions for a 4 week duration. Cumulative copper release in both cell media (0.84 ± 0.21%) and PBS (0.18 ± 0.01%) accounted for less than 1% of theoretical copper present in the films. In vitro cell studies performed with 3T3-J2 fibroblasts and PHHs did not indicate significant toxicity, providing further support for the potential implementation of CuBTTri-based materials in biomedical applications.
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