Endosomal escape remains a major barrier to therapeutic delivery, especially for the delivery of vaccines and nucleic acids for gene therapy. To overcome this hurdle, CBNS scientists have developed pH responsive nanoparticles that are designed to release their therapeutic cargo in the acidic endosomal compartments of the cell.
We demonstrated that the molecular weight of the polymers used to assemble these particles plays a crucial role in the ability to induce endosomal escape. Nanoparticles assembled from polymers with a low molecular weight core showed significantly reduced endosomal escape compared to particles with a higher molecular weight core. All the particles in this study had similar size, surface change and disassembly pH, suggesting that interactions of the pH responsive polymer core with the endosomal membrane play an important role in endosomal escape.