Ultrasound energy collapses porphyrin microbubbles (top) into nanoparticles capable of delivering anti-cancer pharmaceuticals into the deepest recesses of tumours. Photo credit: Elizabeth Huynh
If the human body had a building code, most cancerous tumours would qualify as fast and dirty construction that no inspector would approve. Their blood supply is delivered through leaky, poorly fitting vessels and the surrounding tissue does a terrible job of draining lymphatic fluid. On the other hand, these same shortcomings also create a glaring transport anomaly within the body that turns out to be a veritable magnet for drug molecules, which have no problem making their way to this target.
The trouble starts when this medicine tries to penetrate the tumour itself. Ideally a toxic agent make its way deep within the structure for the greatest effect but getting there has proved challenging. Gang Zheng and his colleagues at Toronto’s Princess Margaret Cancer Centre have been able to meet that challenge with a novel application of micrometre scale bubble dynamics.
Several years ago this research team broke new ground in the field of nanomaterials with the discovery of porphysomes, which are spherical, self-assembling nanostructures made up of the naturally occurring organic compound porphyrin. The group has since published more than 20 papers about this discovery and its potential application as a cancer treatment mechanism. “It opened up a gateway to many different kinds of applications,” says Zheng, who describes porphyrin as a highly practical multifunctional building block. Although porphysomes are biocompatible and non-toxic, they can nevertheless destroy diseased tissue by emitting heat after they absorb infrared light from a laser aimed at the tumour. This same process generates a photoacoustic signal that can be used to generate an image of the resulting effect on the tumour. In addition, porphysome fluorescence serves as an effective tag for tracking the performance of drugs that are being used in this same way against cancerous tissue.
In a new paper for Nature Nanotechnology, members of Zheng’s team outline a further dimension of porphyrin’s medicinal potential. When porphyrin lipid-shell microbubbles containing perfluoropropane gas are bombarded by low-frequency ultrasound energy, they burst and release nanoparticles as small as five nanometres in diameter that can readily travel into a tumour’s deepest recesses. This process is further enhanced as the ultrasound creates temporary pores throughout the tumour. “It all takes just seconds,” observes Zheng, adding that acoustic and fluorescent effects also make it possible to capture images of how well this therapy is working.
University of Toronto doctoral student Elizabeth Huynh, the paper’s lead author who will soon start at the Medical Physics Residency Program at Harvard Medical School, admits that she was not sure that microbubbles could be related to nanotechnology. However, she then discovered that microbubbles could be used for both medical imaging and treatment, an insight she credits the multidisciplinary nature of the project. “This study was a joint effort between researchers across the departments of medical biophysics, chemical engineering, and pharmaceutical sciences,” Huynh wrote in an accompanying article for Nature Nanotechnology. “We had to learn to speak each other’s scientific language to explain the concepts and goals of the study and to gain insight from a different field’s perspective on the topic.”