Scientists at Harvard’s Wyss Institute have developed a technique to deliver chemotherapy to the lungs using red blood cells. The method involves binding chemotherapy-loaded nanoparticles to red blood cells, which are then injected into the bloodstream. Once the red blood cells reach the lungs they have to squeeze through the small capillaries and the resulting shear force removes the nanoparticles, which can then enter cells within the lungs. The researchers hope that the technique could help treat lung metastases with increased efficacy and reduced side-effects, compared with conventional chemotherapy.
Tiny ELeCt nanoparticles are bound to red blood cells in this SEM image, and shear off into target organs when the blood cells make their tight squeeze through the organs’ capillaries. Credit: Wyss Institute at Harvard University
Researchers in the past have used nanoparticles to reduce the adverse side-effects and increase the effectiveness of chemotherapy. However, this has met with mixed success, with one of the major hurdles being a lack of nanoparticle accumulation at tumor sites and rapid nanoparticle clearance by the liver and spleen. The Harvard researchers now used a “trojan horse” technique, where the body’s own cells transport nanoparticles, to deliver chemotherapy to lung metastases.
They have called the technique erythrocyte-leveraged chemotherapy (ELeCt). “30-55% of patients with advanced cancer have metastasis to the lung, due to its large number of capillaries, and there is currently no treatment for lung metastasis itself,” explained Zongmin Zhao, a researcher involved in the study. “ELeCt exploits those same blood vessels to effectively deliver drugs that fight lung metastasis, and has strong potential to be developed into a clinical treatment.”
So far, the researchers have tested their system in mice. They created nanoparticles loaded with doxorubicin, a common chemotherapy drug, and incubated them with mouse red blood cells, where the nanoparticles bound to the surface of the cells. When injected into the bloodstream of mice with melanoma metastases in their lungs, the nanoparticles were sheared off the red blood cells when they passed through the narrow capillaries in the lungs. The new system resulted in a 16-fold increase in the amount of doxorubicin in the lungs compared with nanoparticles alone, which resulted in an almost complete inhibition in metastasis and improved survival in the mice.
When free nanoparticles of doxorubicin were given to mice, almost none of it was deposited into the lung cells (left, labeled in blue), while the ELeCt system achieved much greater doxorubicin deposition in metastatic tissue (right, labeled in red). Credit: Wyss Institute at Harvard University
“The most serious side effect of doxorubicin in humans is cardiotoxicity, and based on our experiments, ELeCt can ensure that more of the drug ends up in the lungs rather than in the heart,” said Anvay Ukidve, another researcher involved in the study. “This advance could significantly reduce the danger to cancer patients receiving this drug, and increase its effectiveness against lung tumors.”