Gold nanoshells sensitize tumors to radiation therapy
MedWire News: Local high temperature treatment delivered by gold nanoshells can make breast tumor cells more sensitive to radiation treatment, US study findings indicate.
The nanoshells - made of silica nanoparticles coated with an ultrathin gold layer - accumulate preferentially in tumor cells and cause local heating when activated by an infra-red laser, explain Jeffrey Rosen (Baylor College of Medicine, Houston, Texas) and colleagues.
The nanoshell-induced heating works by preventing breast tumor cells from repairing DNA double-strand breaks induced by ionizing radiation, which results in increased sensitivity to radiation, the team found.
They injected the gold nanoshells intravenously into mice harboring triple-negative-like mammary tumors and then treated them with 6 Gy of ionizing radiation followed by laser-activated local hyperthermia for 20 minutes at 42°C. Mice that received radiation-only, hyperthermia-only, and a mock treatment were used as comparators.
Two days after treatment, cells derived from the tumors treated with ionizing radiation plus hyperthermia exhibited both a marked decrease in tumorigenicity and a more differentiated tumor phenotype than mock- and radiation-treated tumors, report the researchers in the journal Science Translational Medicine.
To determine whether the tumors retained their tumorigenic properties after treatment, the team then transplanted treated tumor cells into syngeneic recipient mice. They found that cells initially treated with radiation only were more tumorigenic than mock-treated cells.
In contrast, there was a significant decrease in tumor formation in mice that received the dual-treated cells compared with those that received the mock-treated cells.
When the experiment was repeated using human breast tumor biopsy samples propagated in mice, the researchers once again found that the nanoshell-induced heating rendered the human breast tumors much more sensitive to ionizing radiation.
"Together, these data suggest that ionizing radiation plus hyperthermia decreases the tumorigenicity of residual tumor cells and that the surviving cells form tumors that have pathologic signs of histological differentiation with a less aggressive phenotype than either the mock-treated tumors or the tumors treated with sublethal doses of radiation," write Rosen and co-authors.
"Radiation and hyperthermia may be effective in part because this combination simultaneously affects multiple cellular components by altering protein function, influencing multiple survival pathways, and delaying the DNA damage response," they conclude.
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By Laura Dean