Cancer stem cells are no match for researchers at Ohio State University, University of Texas MD Anderson Cancer Center, and other institutions involved in a study recently published in Technology. The team recognized that cryoablation is an effective minimally invasive surgical technology to treat cancerous tumors, but that no one had investigated its effects on cancer stem cells, which are capable of reinitiating tumor growth after chemotherapy treatment. To address this issue, they investigated cryoablation combined with drug treatment to eliminate cancer stem cells in a biomimetic 3D mammosphere model.
Cryoablation involves freezing diseased tissue to subzero temperatures to irreversibly damage tissue without destroying the inflicted organ or leaving noticeable scar formation. However, it probably does not eliminate all diseased cells, and if cancer stem cells are among the remaining cells, tumors may redevelop.
Conventional cancer drug treatment with, for example, doxirubicin (DOX), can be less effective than desired due to poor uptake of the drug by cancer cells. To mitigate this observation, the research team encapsulated DOX in nanoparticles and delivered them along with applied cryoablation. They were able to almost completely eliminate CD44+ CD133+ cancer stem cells by reducing their prevalence in their biomimetic model from 16.6% to 0.6%. “The nanoparticles used in this study were optimized for effective drug delivery,” said Wei Rao, Ph.D., lead author of the paper at Ohio State. The nanoparticles’ optimal uptake can be attributed to the high electrostatic affinity between the positively charged nanoparticles and the negatively charged cell plasma membrane, which facilitated endocytosis of the encapsulated DOX by the cancer stem cells. Free DOX combined with cryoablation was not as effective in reducing the number of cancer stem cells.
“This novel combined therapy of cryoablation and nanodrug is a significant step forward in improving the safety and efficacy of fighting against cancer. Our study provides the first account of minimizing cancer recurrence by destroying the cancer stem-like cells in the field of cryoablation for cancer treatment.” said senior author Xiaoming He, Ph.D., from Ohio State. “It is valuable to facilitate the clinical applications of cryoablation by eliminating the root of cancer resistance — the cancer stem-like cells.”