Ion channel decorated liposomes

Stealth liposomes are promising nanomedicine tools for bringing cytotoxic drugs to their target. However, the release of a drug only at the target has remained elusive. We engineered a natural sensory ion channel into a stimulus-sensitive nanovalve and incorporated it into the stealth liposomes. In the absence of the stimulus, e.g. during circulation in the blood, the nanovalve stays closed. However, upon sensing a target-specific stimulus, it opens a large, non-selective aqueous pore on the surface of the liposome and releases the drug payload at once. Currently, the nanovalve detects the pH differences in the physiological pH range with 0.2 pH unit precision in vivo and the wavelength of the light. It can be engineered to detect other signals. Even though such triggered drug delivery system is very advantageous, the bacterial origin of the ion channel poses a risk of immunogenicity. We addressed this point by producing alternative nanovalves from the homologues ion channels from different organisms. After predicting the potential immunogenicity of these ion channels in silico, the relative immunogenicity of our liposomal formulations with individual ion channels were tested by Dendritic cell-T cell assay from ProImmune. We obtained very promising results, which will be discussed in the meeting..