Non-covalent assembly of albumin nanoparticles by hydroxyl radical: A possible mechanism of the nab technology and a one-step green method to produce protein nanocarriers

Abstract

Protein-based nanoparticles (NPs), especially albumin NPs, are effective and safe drug carriers. Non-covalently assembled albumin NPs prepared by the nanoparticle albumin-bound (nab) technology possess higher tumor targeting efficiency compared to crosslinked albumin NPs. However, the production process of protein NPs by the nab technology is rather complicated and involves toxic chemicals. Moreover, the mechanisms behind the assembly of albumin induced by the nab technology are far from elucidated. We hypothesized that hydroxyl radical may facilitate the formation of protein NPs prepared by the nab technology. Based on that, a novel and green method was developed to produce protein NPs by controlled hydroxyl radical oxidation via Fenton reaction through one-step mixing. The resulted bovine serum albumin (BSA) NPs were revealed as a non-covalent assembly of BSA molecules with hydrophobic interaction as the driven force for the NPs formation. The Fenton method of BSA NPs production was facile to produce the lipophilic drug paclitaxel (PTX) loaded BSA NPs (PTX@BSA NPs), which exhibited promising antitumor efficacy, pharmacokinetic and safety profiles. Besides BSA, the Fenton method was applicable to other proteins including casein, beta-lactoglobulin and keratin. Thus, the one-step Fenton methodology offers a unique green solution to produce non-crosslinking protein NPs as effective drug carriers for biomedical applications.