Platinum(IV)-chlorotoxin (CTX) conjugates for targeting cancer cells

Cisplatin is one of the most widely used anticancer drugs. Its side effects, however, have motivated researchers to search for equally effective analogs that are better tolerated. Selectively targeting cancer tissue is one promising strategy. For this purpose, a platinum(IV) complex was conjugated to the cancer-targeting peptide chlorotoxin (CTX, TM601) in order to deliver cisplatin selectively to cancer cells. The 1:1 Pt-CTX conjugate was characterized by mass spectrometry and gel electrophoresis. Like most platinum(IV) derivatives, the cytotoxicity of the conjugate was lower in cell culture than that of cisplatin, but greater than those of its Pt(IV) precursor and CTX in several cancer cell lines.

Graphical abstractBy combining a Pt(IV) compound with the cancer-cell targeting peptide CTX in a pro-drug approach, a precursor of the anticancer drug cisplatin can be transported to cancer cells. In cancer cells that express receptors for CTX, cisplatin can thus be released selectively.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A novel Pt(IV) chlorotoxin conjugate was synthesized. ► The 1:1 conjugate was identified by analysis with HPLC, AAS, UV/Vis, SDS-PAGE and TOF-MS. ► In vitro cytotoxicity was increased when compared to the Pt(IV) precursor and CTX. ► In cells with high expression of CTX receptors increase in cytotoxicity was most striking.