pH-triggered morphological change in a self-assembling amphiphilic peptide used as an antitumor drug carrier

The geometry of nanoparticles plays an important role in the process of drug encapsulation and release. In this study, an acid-responsive amphiphilic polypeptide consisting of lysine and leucine was prepared. In neutral media, the amphiphilic peptide L₆K₄ self-assembled to form spherical nanoparticles and encapsulated fat-soluble antitumor drugs. The intratumoral accumulation of the drug-loaded nanoparticles was improved in HeLa cells compared with normal cells. Compared to a neutral environment, increasingly acidic solutions changed the secondary structure of the peptide. In addition, the drug-loaded nanoparticles expanded and decomposed, rapidly releasing the poorly soluble antitumor drug doxorubicin (DOX). In addition, the amphiphilic peptide L₆K₄ had antitumor properties, and the antitumor performance of the combination of L₆K₄ and DOX was better than that of free DOX. Our results indicate that the use of acid responsiveness to induce geometric changes in drug-loaded peptide nanoparticles could be a promising strategy for antitumor drug delivery.