Temporal Controlled Membrane Fusion as a Drug Delivery Tool in Vitro and in Vivo

Membrane fusion results in the transport and mixing of (bio)molecules across otherwise impermeable barriers. In our group, we have reported a new method of delivering drug directly into the cytosol of live cells utilizing... [ view full abstract ]

Membrane fusion results in the transport and mixing of (bio)molecules across otherwise impermeable barriers. In our group, we have reported a new method of delivering drug directly into the cytosol of live cells utilizing targeted membrane fusion between liposomes and live cells. A pair of complementary coiled-coil lipopeptides (CP₄E₄&CP₄K₄) was embedded in the lipid bilayer of liposome and counter cell membrane respectively resulting in targeted membrane fusion with concomitant release of liposome encapsulated cargo. To further regulate the fusion process, we applied steric PEG shielding and rapid, photo-induced de-shielding method to temporal control the whole process. With PEGylation, E₄ peptide on liposome was shielded and the fusion ability with K₄-liposome or K₄-cell was inhibited. However, as soon as light was applied to remove the PEG shielding, the interaction between E₄&K₄ was regained, accompanying fast membrane fusion. With this strategy, the fusion in vivo was also successfully controlled. The original freely circulated PEGylated E₄-liposomes could selectively accumulate at tumor sites modified with K₄ after light-activated removal of the PEG corona. Furthermore, the growth of tumor was successfully suppressed by ingesting the doxorubicin encapsulated in liposomes. In conclusion, by this photo-activated membrane fusion, we could deliver drug in a controlled manner with high efficiency.