Reflecting recent work in the

Hepatocellular carcinoma, HCC, is the sixth most frequent cancer and the second leading cause of death from cancer worldwide. Sorafenib is the most commonly used FDA‐approved systemic drug for treating advanced HCC, but suffers from low efficacy and severe side effects. Thus there is a need for specific chemotherapeutics against HCC.

Cisplatin is an effective chemotherapeutic against many cancer cells but is also toxic to healthy organs.Platinum nanoparticles, PtNPs, are promising alternatives to cisplatin and other platinum‐based complexes. However, previous studies with various cancer cell lines neither showed improved cytotoxicity nor tumor selectivity of PtNPs over cisplatin.

In an article published as the cover article in Angewandte Chemie, researchers in the Wennemers Group, describe the development of Peptide‐stabilized Platinum Nnanoparticles, PtNPs, which have significantly greater toxicity against hepatic cancer cells, HepG2, than against other cancer cells and non‐cancerous liver cells. The peptide H‐Lys‐Pro‐Gly‐dLys‐NH₂ was identified by a combinatorial screening and further optimized to enable the formation of water‐soluble, monodisperse PtNPs with average diameters of 2.5 nm that are stable for years.

In comparison to cisplatin, the peptide‐coated PtNPs are not only more toxic against hepatic cancer cells but have a significantly higher tumor cell selectivity. Cell viability and uptake studies revealed that high cellular uptake and an oxidative environment are key for the selective cytotoxicity of the peptide‐coated PtNPs.