Nanobubbles Deliver Targeted Cancer Drugs Using Ultrasound
Using a combination of polymers that respond to temperature, a research team at the University of Utah has developed a multifunctional nanoparticle that can image tumors using ultrasound and simultaneously deliver cell-damaging energy and anticancer drugs to those tumors. In addition, these nanoparticles appear to act specifically on tumors and not on healthy tissue.
Reporting its work in the journal Ultrasonics, a research team headed by Natalya Rapoport, D.Sc., describes its development of nanoparticles designed to turn into larger microscale bubbles at body temperature. These nanoparticles are made of perfluorocarbons, which interact strongly with ultrasound, and small amounts of two different biocompatible polymers derived from poly(ethyleneglycol) (PEG). By adjusting the relative amounts of the two PEG-based polymers, the investigators found that they could create nanoparticles that were stable at room temperature but that at body temperature would eventually combine to create ultrasound-responsive microbubbles. The researchers also demonstrated that they could load therapeutic doses of doxorubicin, a potent anticancer drug, into these nanoparticles and that the drug remained entrapped when the transition from nanoparticles to microbubbles occurred.
When injected into tumor-bearing mice, the nanoparticles retain their size long enough to travel to tumors and seep out of the leaky blood vessels that surround solid tumors. Once in the tumors, the nanoparticles begin coalescing into larger microbubbles that are then readily visible using standard ultrasound imaging instruments. Once tumor imaging is complete, focused ultrasound is then directed at the tumors, triggering drug release within the tumors. In addition, ultrasound energy causes the microbubbles to explode, which can damage nearby cancer cell membranes and further enhance drug uptake. Tumor-bearing mice treated with these nanoparticles showed dramatic tumor regression after two treatments spread 1 week apart.
This work is detailed in the paper “Drug-Loaded Nano/Microbubbles for Combining Ultrasonography and Targeted Chemotherapy.” An abstract of this paper is available through PubMed.