Abstract
Cisplatin (cis-diamminedichloroplatinum (II), CDDP) is a chemotherapeutic drug widely used against many solid tumors. A pharmacokinetics study found that CDDP can bind to human serum albumin (HSA), which is the most abundant plasma protein in serum. HSA has the advantage of being a nanocarrier and can accumulate in tumors by passive targeting and active targeting mediated by the secreted protein acidic and rich in cysteine (SPARC). In this study, we investigated the possibility of using a CDDP–HSA complex (HSA–CDDP) as a SPARC-mediated therapeutic agent. To investigate the HSA-dependent therapeutic effect of HSA–CDDP, we used two types of U87MG glioma cells that express SPARC differently. HSA–CDDP was highly taken up in SPARC expressing cells and this uptake was enhanced with exogenous SPARC treatment in cells with low expression of SPARC. The cytotoxicity of HSA–CDDP was also higher in SPARC-expressing cells. In the tumor model, HSA–CDDP showed a similar tumor growth and survival rate to CDDP only in SPARC-expressing tumor models. The biosafety test indicated that HSA–CDDP was less nephrotoxic than CDDP, based on blood markers and histopathology examination. Our findings show that HSA–CDDP has the potential to be a novel therapeutic agent for SPARC-expressing tumors, enhancing the tumor targeting effect by HSA and reducing the nephrotoxicity of CDDP.
Highlights
Cisplatin (cis-diamminedichloroplatinum (II), CDDP) is a chemotherapeutic drug widely used against many solid tumors [1,2]
We investigated the potential of Human serum albumin (HSA)–CDDP as a therapeutic agent for a glioblastoma model and focused on the secreted protein acidic and rich in cysteine (SPARC)-mediated efficacy and safety
The proportion of CDDP per mole of HSA was calculated from the molecular weight difference between HSA–CDDP and HSA
Summary
Cisplatin (cis-diamminedichloroplatinum (II), CDDP) is a chemotherapeutic drug widely used against many solid tumors [1,2]. It was first described in 1845, and the antitumor potential of CDDP was first discovered in the 1960s [3]. HSA is the most abundant plasma protein with a serum concentration of 40–45 g/L in healthy adults. It has the advantages of being a nanocarrier, water-soluble and biocompatible, and has a long half-life in blood and low toxicity [7,8]. By binding CDDP to HSA, HSA can inhibit the excretion of CDDP through the kidney
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have