Develop liposome-based drug carriers in response to tumour microenvironment

Abstract

Hama is currently leading a team of scientists at Kyoto Pharmaceutical University who are attempting to develop a novel solution to drug targeting in cancer. They have overcome the key problem of drug targeting by specifically targeting correct concentrations of the tumour. ‘This novel targeting method has arisen out the team’s research investigating the tumour microenvironment (TM),’ notes Hama. This is defined as the specific immediate environment in which the tumour is found and has distinct properties from the surrounding tissue. Hama and his team realised that the unique properties of the TM could be used to differentiate the cancerous areas from the rest of the body. ‘Our group has been developing some drug carriers that respond to the tumour microenvironment,’ he says. ‘These carriers can achieve effective intracellular delivery of drugs by passing various biological barriers, and are expected as a useful carrier for the cancer detection and therapy.’ The team’s design revolves around the unique chemical conditions within the tumour microenvironment. The TM is very slightly acidic compared to most other tissues. Typically, most cells need to be at a neutral pH (7.2-7.4), however, the TM is such that the pH within it rests at 6.5. This provides both a problem and an opportunity. ‘The problem is that, within, cancerous cells, the pH remains neutral and so it is necessary to navigate this change in pH,’ observes Hama. ‘However, this difference – specific to the TM – also presents a method through which tumours can be differentiated from the surrounding tissue.’ They have designed a coating for liposomes that allow them to switch their charge when faced with the lower pH of the TM. This switch is mediated by the presence of specific amino acid residues within a small peptide attached to the liposome. ‘By interspersing the peptide with a mix of histidine and glutamic acid residues, we are able to create structure that have a negative charge in the bloodstream and elsewhere in the body and a positive charge in the TM,’ Hama outlines.