Cancer-targeting protein bullet
Small protein molecules that can selectively penetrate cancer cells but leave healthy tissue untouched have been developed by Japanese scientists.
A major goal for cancer therapy is the ability to target treatments only to the malignant cells, sparing patients side-effects caused when harm is done to healthy tissues. But "magic bullets" capable of operating in this way have previously been hard to come by. Now a discovery announced this week by Nagoya University researcher Masayuki Matsushita and his colleagues could change that.
The team have been working on molecules called cell-penetrating peptides (CPPs). These are small protein chains that are actively taken up by cells, and if they're coupled to a cargo, like a coloured marker or a drug molecule, this is also pulled inside the cell at the same time. To identify CPPs that could target cancers exclusively, the team took short, random sequences of genetic material called messenger RNA attached to a special linker molecule. Also bound to this linker molecule was the corresponding protein that would be produced were that genetic sequence to be read inside a cell. These molecules were then sprinkled onto a dish of cultured cells. If the attached protein behaved as a CPP, the protein and the linked genetic material would be taken up by the cells and then could be isolated, copied and turned into more of the proteins linked to their corresponding messenger RNAs.
After repeating this process more than 5 times, the team assembled a family of proteins that appeared to function as efficient CPPs. These were then linked to coloured markers so that any cells that took them up would be labelled accordingly, and they were tested on a range of normal and human cancer cells in culture.
Of the 47 potential CPPs tested, 10 appeared to enter cancer cells exclusively; of these, the majority were even selective for different types of cancer cell. The team then tested two of the new CPPs in mice that had been injected with human cancer cells. Tumours, but not healthy tissue, in the animals could be labelled by the proteins. And when an anti-cancer gene was coupled to the CPP and injected into tumour-bearing mice, the animals survived for significantly longer and showed significantly reduced cancer spread compared with control animals.
According to the team, writing in their paper in Nature Communications, "These cell-penetrating peptides are potentially useful for the efficient targeting of human neoplasms in a tumour origin-dependent manner, and provide a framework for the development of peptide-based anti-tumour technologies."