Self-Assembling paclitaxel Nanofibers for Controlled Drug Release

Peptide-drug conjugations have been of great interest in recent years for cancer chemotherapy. The 3D self-assembly process of peptide hydrogel is governed by many different types of forces, which we can carefully manipulate to control the pharmacokinetics of the drug. However, the critical role of hydrophobicity and Ï?-Ï? interaction in the morphology has not been fully explored. Here we have developed monodisperse drug amphiphiles that self-assemble into helical super-coiled filamentous structures. We conjugated the hydrophobic drug Paclitaxel to the peptide sequence FFFRGDR via a biodegradable disulfylbutyrate (buSS) linker. The peptide sequence incorporates several aromatic amino acids Phenylalanine and the tumor penetrating peptide RGD. The Ï?-Ï? interaction and steric effect causes torsional strain in the β-sheets and thus the right hand twisting, leading to the â??super coilâ? nanofilaments. These helical nanofibers have been shown to have enhanced stability compared to straight peptide nanofibers as shown by a lower critical micellization concentration (CMC). They have a slower and more sustained release of the drug content. This suggests possibility for less frequent dosing due to the slower release and smaller fluctuation in the concentration of the drug, which is beneficial to the patients. We believe this strategy can be extended to fabricate morphologies and stability of nanostructures with Ï?-Ï? interactions and hydrophobic interactions. These nanofilaments with various structures and mechanical properties can be used for hydrogel formation with different anti-cancer drug release rates, leading to new opportunities for the local treatment and drug delivery for multiple cancer chemotherapy.