A major obstacle in effectively treating certain cancers is a condition known as hypoxia, where tumor cells are starved of oxygen and consequently become resistant to conventional treatments like radiation and chemotherapy. When this happens in practice, a doctor typically increases the radiation dose or the concentration of the chemotherapy drug, which often adversely affects the patient.
University of Illinois at Urbana-Champaign Bioengineering Professor Joseph Irudayaraj and his team have recently developed a nanotechnology-based platform that delivers oxygen to the diseased cells and helps restore the effectiveness of the cancer treatment.
“Cells in the hypoxic state are two- to three-times less receptive to treatments like radiation and chemotherapy,” noted Irudayaraj, the Founder Professor in Bioengineering, who holds appointments in the Carl Woese Institute for Genomic Biology and Micro + Nanotechnology Lab on campus. “If our technology can even decrease the radiation dose by 20%, then that’s effective.”
Irudayaraj and his research team created injectable nano-size oxygen bubbles made of FDA-approved cellulose compounds that are bio-compatible. In a study published in Nature Scientific Reports, they injected the 80-500 nanometer-size nanobubbles in mouse models with cervical cancer (HeLa) and bladder cancer (MB49) tumors.
Exposed to the acidic microenvironment around and inside the tumor cells or triggered by ultrasound, the nanobubble shells are disintegrated, releasing oxygen and destabilizing the hypoxia-adaptive pathways. As a result, the oxygen nanobubbles altered the epigenetic state of the cell cycle-related genes and slowed the spread of the cancer cells.
According to Irudayaraj, this work was the first demonstration of the safe and successful implementation of oxygen nanobubbles less than 100 nm, and it provides the first evidence of the therapeutic potential of the nanobubbles in reverting hypoxic tumor regions. The nanobubble technology may eventually be an adjuvant for treating lymphoma and bladder, prostate, and breast cancers.
“The advantage of our nano-sized bubbles is they can penetrate deeper into the tumor vasculature,” said Irudayaraj, who conducted this work while still a faculty member at Purdue University earlier this year. “As we continue to develop this technology at Illinois, we plan to collaborate with the College of Veterinary Medicine to develop it for canine models and ultimately for human trials.”
Another advantage of Irudayaraj’s nanobubble technology is that it can act as a contrast agent for ultrasound imaging, essentially producing more detailed images of tumors. In addition, the nanobubbles could be filled with a therapeutic drug and directed to release the medicine deep inside a tumor using ultrasound.
This work was funded by the National Institutes of Health through the Purdue University Center for Cancer Research and Indiana Clinical and Translational Sciences Institute, and by a W.M. Keck Foundation grant.
The full title and authors of the paper are: “Oxygen nanobubbles revert hypoxia by methylation programming,” Pushpak Bhandari, Yi Cui, Bennett Elzey, Craig Goergen, Christopher Long, and Joseph Irudayaraj, Nature Scientific Reports.
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For more information, contact Joseph Irudayaraj at (217) 300-0525, or jirudaya@illinois.edu