Toxicity Study of Therapeutically Active Copper Nitroprusside Analogue Nanoparticles: An In Vitro and In Vivo Approaches.

Copper-based nanomedicines have broader applications in the biomedical sector because of their unique fundamental properties. Very recently, our group has designed and synthesized new copper nitroprusside analogue nanoparticles (CuNPANP in vitro and in vivo) anticancer therapy in both breast cancer and melanoma. The toxicity study of these therapeutically active nanomedicines in small and large animals is a prerequisite before their clinical translation. In the present manuscript, detailed toxicity studies of CuNPANP are demonstrated through various in vitro and in vivo studies. Initially, the biocompatible nature of the CuNPANP has been established through several in vitro assays (cell viability assay, cell cycle study, apoptosis analysis, and determination of reactive oxygen species using DCFDA) in RAW 264.7 cells. Further, the noninflammatory nature of the nanoparticles toward RAW 264.7 cells has been investigated through immunocytochemistry (COX-2 staining) and Western blot analysis. The in vivo toxicity studies of CuNPANP have been performed in a BALB/c mouse (male and female) model using therapeutic doses (1 and 5 mg kg-1 body weight (b.w) in a time-dependent manner (30, 60, and 120 days). There were no significant changes observed in different body parameters (body weight, feed consumption, and relative organ weight) of the mice and no major alterations were found in blood hematology and serum biochemical measurements, while we compare the CuNPANP-treated groups with the UT group. Furthermore, the histopathological examination of male mice group upon 30, 60, and 120 days exposure reveals the biocompatibility of CuNPANP. Further, the biodistribution study reveals the distribution of copper in vital organs. Altogether, the results demonstrate the nontoxicity and biocompatibility of the nanomaterials.