Assembly mechanism-instructed precision nanocarriers: Esox lucius apoferritin for hydrophilic or hydrophobic drug loading and smart release.
TL;DR
It is demonstrated that apo-Fn undergoes controlled disassembly under mild acidic conditions, and efficiently reassembles upon neutralization or urea removal, and efficiently reassembles upon neutralization or urea removal.
Abstract
Ferritin (Fn) nanocages offer significant potential as drug delivery vehicles due to their biocompatibility, well-defined structure, and inherent targeting capabilities. In this study, we isolated Fn from the liver of Esox lucius and prepared its apo-form (apo-Fn) to engineer its reversible disassembly/reassembly for drug encapsulation. We demonstrated that apo-Fn undergoes controlled disassembly under mild acidic conditions (pH 2.0-4.0) or 4 M urea, and efficiently reassembles upon neutralization or urea removal. Thermal treatment below 55 °C also facilitated reversible structural transitions. Based on these properties, three loading strategies were developed. The temperature-gradient method was optimal for hydrophilic drugs (doxorubicin and phenytoin), while the urea-gradient method achieved 42.18% encapsulation for hydrophobic paclitaxel. The resulting formulations showed uniform size, colloidal stability, and minimal leakage at pH 7.4, but exhibited rapid release at acidic pH 5.0. Furthermore, apo-Fn showed high biocompatibility (> 90% cell viability) and exerted intrinsic anti-inflammatory effects by modulating macrophage polarization. This study highlights piscine apo-Fn as a promising platform for targeted drug delivery.