Targeted radiation-based therapies for treating cancerous tumours such as 'boron neutron capture therapy' (BNCT), rely on the efficient and effective delivery of the capture agent (in this case, boron) to the tumour. The agent must collect in the tumour in high enough concentrations to trigger an effective reaction during thermal neutron irradiation.
Delivering the agent to tumours safely, while limiting the chances of it being distributed in the bloodstream and major organs, is a major challenge. Hiroyuki Nakamura and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, decided to test the ability of a common blood plasma protein known as albumin to carry boron to tumours during BNCT.
Albumin flows readily to and accumulates in malignant tissues; in fact, it is a major source of nutrition for growing tumours. Tumours therefore attract albumin, making the protein an ideal candidate for carrying drugs - it has already been used as a drug carrier for breast, lung and pancreatic cancers. However, its ability to transport boron for BNCT remains untested.
This image shows efficient BNCT effects of MID-AC against tumors of mice. Credit: 2016 Hiroyuki Nakamura at Tokyo Institute of Technology
Nakamura's team developed a tiny capsule, made from maleimide-functionalized closo-dodecaborate (MID), and trialled its ability to bind with albumin and to carry boron. They found that MID successfully binds with both cysteine and lysine residues in albumin, creating a stable carrier for boron that the team called MID-AC.
They tested MID-AC on 26 tumour-bearing mice. The team found that the boron concentrated highly and efficiently in tumours; the active uptake of boron by the albumin led to double the concentration of boron reaching tumours than previous systems. Levels of boron in the bloodstream and organs were very low, indicating a viable targeted delivery system. Thermal irradiation was then carried out on the mice, and led to the significant suppression of tumour growth even at low boron levels.
This technique could limit existing problems of using blood-based products in cancer treatment. Albumin could be taken from patients in hospital prior to treatment, then used in MID-AC to carry boron to tumours in the patients' own bodies. This will limit contamination and encourage the acceptance of the system by the patients' immune systems.
source: Tokyo Institute of Technology