Engineered Blood?

Nanoparticles bearing designed peptides in circulation selectively clot tumor vessels and amplify their own accumulation at that site, according to recent finding (PNAS 2007, 104, 932-936. DOI: 10.1073/pnas.0610298104).

The researcher first found a short peptide Cys-Arg-Glu-Lys-Ala (CRECK) that binds clotted plasma proteins in tumors. Then they attacth this peptides to iron oxide nanoparticles with diameter of 50 nm. The nanoparticles were found to accumulate only at tumor site and liver, but cause clotting in tumor vessels only, which involved no platelets.

The interstitial spaces of tumor contain fibrin and proteins that become cross-linked to fibrin in blood clotting. The presence of these products in tumors, but not in normal tissues, is thought to be a result of leakiness of tumor vessels, which allows plasma proteins to enter from the blood into tumor tissue, where the leaked fibrinogen is converted to fibrin by tissue procoagulant factors. The clotting creates new binding sites that can be identified and accessed with synthetic peptides like CREKA, with which the nanoparticles once modified can bind and induce localized tumor clotting. But the detailed mechanism of clotting is yet to be study, and it is unknown whether these plasma protein-binding nanoparticles would also affect other regions of pathological clotting activity in the body (e.g., wounds) and induce additional clotting at such sites.

John Salzi's recent science fiction Old Man's War describes the possibility to engineer every piece of tissue in human body into high-performance materials. As for the circulation system, the blood is in fact a solution of smart nanoparticles that have ultra-high capability of oxygen delivery and clot within seconds. Tumor homing is nice but blood engineering is more exciting. The next step of this study should point to faster clotting and higher oxygen loading features of well-defined nanoparticles.