Could Cisplatin Loading on Biosynthesized Silver Nanoparticles Improve Its Therapeutic Efficacy on Human Prostate Cancer Cell Line and Reduce Its In Vivo Nephrotoxic Effects?

Abstract

Nanotechnology is a possible solution to the drawbacks of cancer therapy because it decreases the clinical side effects of chemotherapeutic drugs and increases their clinical activity. Thus, this work compared the in vitro cytotoxic activity and in vivo side effects of cisplatin (CP) with those of CP-loaded green silver nanoparticles (CP-AgNPs). The cytotoxic activity of CP, green AgNPs, and CP-AgNPs against PC-3, a human prostate cancer cell line, was assessed using MTT assay. CP-AgNPs had a superior cytotoxic effect on PC-3 cells with a 50% inhibition of viability (IC50) of 27.05 μg/mL, followed by CP with an IC50 of 57.64 μg/mL and AgNPs with an IC50 125.4 μg/mL. To evaluate in vivo side effects, 40 male adult Wistar rats were assigned into four groups and intraperitoneally injected with normal saline (control), CP (2.5 mg/kg body weight), green AgNPs (0.1 mL/kg body weight), and CP-AgNPs (2.5 mg/kg body weight). Intraperitoneal CP injection caused a substantial reduction in erythrocyte and leukocyte counts and hemoglobin concentration and a marked increase in urea and creatinine levels and disturbed the renal oxidant/antioxidant status. Furthermore, it caused noticeable structural alterations and significant upregulation of renal Bax and caspase-3 mRNA along with a significant downregulation of B-cell lymphoma 2 mRNA expressions. The loading of CP on green AgNPs significantly relieved the CP-induced pathological alterations and considerably enhanced its therapeutic effectiveness on PC-3 cells. These outcomes reflect the possible use of CP-AgNPs as a more efficient and safer anticancer agent than free CP.