Advances in cytosolic drug delivery

Nanoparticles (particles smaller than 100 nm where materials display different properties than at the bulk state) are frequently used in nanomedicine for drug delivery and other purposes. The sophistication and specificity of nanoparticle use is growing, particularly for delivering drugs past the lipid bilayer barrier of the cell wall to the inside of cells (cytosolic drug delivery) where they can target biophysical processes more easily. Two advances focus on cytosolic drug delivery, using light and peptides to break the endosomes (carrying vehicles) to release drugs directly into the cytosol.

1) Light-mediated endosomal breakage
One advance is in the development of nanoparticles (size-tunable (30-200 nm) highly monodispersed mesoporous silica nanoparticles) that can be loaded with a variety of compounds and released into the cytosol via light-mediated endosomal breakage, as illustrated in Figure 1 (Febvay et al, Nano Lett, 2010).

Figure 1: Nanoparticle cargo discharge through light-activation.

2) GALA peptide endosomal breakage
A second advance is in cytosolic drug delivery with nanoparticles using a peptide, GALA, to encourage endosomal breakage. GALA (comprised of repeating sequences of Glu-Ala-Leu-Ala) mimics the function of viral fusion protein sequences that mediate escape of virus genes from endosomes (Nakase et al, Methods Mol Biol, 2011).