Effect of Protein Corona on The Specificity and Efficacy of Nanobioconjugates to Treat Intracellular Infections.

Encapsulating drugs into functionalized nanoparticles (NPs) is an alternative to reach the specific therapeutic target with lower doses. However, when the NPs are in contact with physiological media, proteins adsorb on their surfaces, forming the biomolecular layer named protein-corona (PC), acquiring a distinct biological identity that alters their interactions with cells. In this regard, we encapsulated itraconazole (ITZ), an antifungal agent, into PEGylated and/or functionalized NPs with high specificity for macrophages and evaluated how the PC impacted their cell uptake and antifungal effect. Our results of the Minimum-Inhibitory-Concentration (MIC) and Colony-Forming-Units (CFU) assays demonstrated that encapsulated ITZ into poly(ethylene-glycol) (PEG) NPs improved the antifungal effect compared with NPs lacking PEGylation. The antifungal improvement can be related to the synergistic-effect of the encapsulated ITZ and NPs composition and the reduction of PC formation in PEG-NPs. Functionalized NPs with anti-F4/80- and anti-MARCO- antibodies, or mannose without PEG and treated with PC showed an improved uptake but, in the presence of PEG, significantly reduced the endocytosis, dominating the stealth effect from PEG. Therefore, the PC plays a crucial role in the nanosystem uptake and antifungal effects, which suggests the imperative need for in vivo model studies to evaluate the effect of PC in the specificity and biodistribution. This article is protected by copyright. All rights reserved.