pH-Triggered Geometrical Shape Switching of a Cationic Peptide Nanoparticle for Cellular Uptake and Drug Delivery

Abstract The geometry of nanoparticles plays an important role in their performance as drug carriers. However, the pH-triggered geometrical shape switching of a cationic peptide consisting of isoleucine and lysine is seldom reported. In this work, we designed a cationic peptide with acid reactivity that can be loaded with the poorly soluble antitumor drug (doxorubicin (DOX)) to enhance tumor cell uptake and drug delivery. In a weakly acidic environment, a large portion of random coil structures formed, which subsequently led to nanoparticle destruction and rapid DOX release. In vitro studies demonstrated that this cationic peptide exhibits low toxicity to normal cells. The amount of DOX-encapsulating peptide nanoparticles taken up by tumor cells was greater than that taken up by normal cells. Our results indicated that the use of a weakly acidic microenvironment to induce geometric shape switching in drug-loaded peptide nanoparticles should be a promising strategy for antitumor drug delivery.