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 a protein corona (PC) biomolecular layer, acquiring a distinct biological identity that alters their interactions with cells. Itraconazole (ITZ), an antifungal agent, is encapsulated into PEGylated and/or functionalized NPs with high specificity for macrophages. It is evaluated how the PC impacts their cell uptake and antifungal effect. The minimum inhibitory concentration and colony-forming unit assays demonstrate that encapsulated ITZ into poly(ethylene glycol) (PEG) NPs improves the antifungal effect compared with NPs lacking PEGylation. The 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, show an improved uptake but, in the presence of PEG, significantly reduce 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 need for in vivo model studies to evaluate the effect of PC in the specificity and biodistribution. Itraconazole is encapsulated in functionalized nanoparticles to assess the impact of the protein corona on its cellular uptake and antifungal effect. The PEGylated nanoparticles with itraconazole improve the antifungal effect due to the reduced adsorption of nonspecific proteins, increasing drug release. While functionalized nanoparticles with antibodies or mannose show greater cellular uptake, the presence of poly(ethylene-glycol) (PEG) reduces the adsorption, dominating the PEG stealth effect.image

Automated summary

Encapsulation of itraconazole in functionalized nanoparticles allows for targeted therapy with reduced doses. Protein corona formation on the surfaces of nanoparticles affects their interactions with cells. PEGylated nanoparticles improve the antifungal effect of itraconazole by reducing non-specific protein adsorption.