DMSO-mediated reversible disassembly-reassembly of ferritin nanocages for efficient encapsulation and glioma-targeted delivery of hydrophobic drug

Abstract

Ferritin, as a highly promising protein nanocage, has been widely applied in the fields of vaccines, nanoparticle synthesis, drug delivery, and so forth. Recently, ferritin-based drug delivery has been made remarkable progress, nevertheless, enhancing drug loading efficiency and yield still desired. Here, a novel dis/reassembly method for ferritin drugs loading is proposed using dimethyl sulfoxide (DMSO). Briefly, dried HFn (H-ferritin) is dissolved with DMSO to disrupt its cage structures, then the disassembled HFn is diluted in HEPES to reassemble into the 24-mer cage, while simultaneously could encage chemotherapeutic drugs inside the cage. The results shown that this disassembly-reassembly method achieves a recovery rate of HFn exceeding 80 % and a drug loading capacity of 65.3 Dox per cage, surpassing previously reported disassembly-reassembly methods. Importantly, the new prepared HFn-Dox can target tumor in vitro and in vivo. And the anticancer effects of HFn-Dox also has been evaluated with in situ glioma using both MR imaging and in vivo fluorescence imaging methods, founding their superior tumor growth inhibition in comparison with free Dox. Thus, the DMSO-mediated dis/reassembly drug loading method of ferritin provides a new potential approach to the preparation of ferritin-based drugs for tumor diagnosis and therapy.