Boronic acid conjugated peptide amphiphile systems for controlled drug release

Abstract

Targeted cancer drug delivery is still under investigation and scientists have been focusing on major differences between healthy and cancer tissue to develop novel effective therapies. The cancer microenvironment has different physiological properties than the healthy tissues, for instance, it has more acidic pH, and much of the attention has been given to developing stimuli responsive agents for targeted drug delivery applications. Boronic acid is one of the most well-known stimuli responsive molecule which can form reversible covalent bonds with vicinal diols such as saccharide or catechol, that achieves targeted cancer drug release in a pH dependent manner. At neutral pH, the bond formation is triggered; however, these bonds become weaker at slightly acidic environment. Boronic acid conjugated polymers have been frequently preferred for doxorubicin encapsulation, which is a widely used chemotherapeutic drug utilized to treat several cancer types. In this study, boronic acid and DOPA conjugated peptide amphiphiles were used as a biocompatible and biodegradable alternative to polymeric systems. Peptide amphiphiles self assemble to form peptide nanofibers via noncovalent interactions, such as hydrogen bonding, hydrophobic interactions, van der Waals forces and electrostatic interactions, where boronic acid/DOPA units remain on the exterior part of the nanofibers. In addition to noncovalent interactions, at physiological pH, boronic acid and DOPA moieties on the peptide surface form reversible covalent complexes, resulting in improved hydrogel strength, self-healing capacity and entrapment of doxorubicin inside the 3D-network. On the other hand, under acidic conditions, these interactions weaken and doxorubicin release is accelerated at tumor site. Reversible covalent interaction, secondary structure, morphological, mechanical, release profile analysis were performed on the system. Results showed that this system exhibits promising features that can be used for therapeutic applications.