Tiny drug-delivery vehicles never actually escape their cellular cages, even though doctors have believed they were breaking out for decades.

Proton-sponge polymers were long thought to act like microscopic explosives that burst open the lysosome to release medicine into the cell. This study shows the nanoparticles actually remain trapped inside the cell's waste-disposal unit indefinitely. Only the small drug molecules leak out through a destabilized membrane like water through a sieve. This discovery explains why many nanomedicines fail in clinical trials because the delivery vehicles are getting stuck at the finish line. Engineers can now stop trying to force the entire vehicle out and instead focus on making the cargo leak more efficiently. This shift in perspective will likely lead to much more effective gene therapies and cancer treatments.