Composite Protein Crystals doped with Metal Nanoparticles as a complete antibacterial system

The increasing prevalence of antimicrobial resistance is challenging the global healthcare system (1). The overuse and inappropriate use of antibiotics have resulted in pathogens with multi-drug resistance, leading the world to a pre-antibiotic era (2,3).

Therefore, the objective of this work is to develop an innovative drug delivery vehicle capable of addressing multidrug-resistant bacterial infections by converting them into an active support. To do this, we have encapsulated silver or gold metallic nanoparticles (MNP) in cross-linked lysozyme crystals. These crystals-composites of proteins and MNPs will behave as release vehicles capable of dealing with infections thanks to their dual composition and the control of the release rate by the degree of cross-linking of the crystals. We anticipate that this synergistic antimicrobial material may be an excellent strategy to combat biofilm formation.

To obtain this material, we followed a bottom-up protocol in which MNPs were firstly obtained in a peptide hydrogel of Fmoc-MF, which contains specific interaction sites with the MNPs to increase their stability during crystallization step. These metallogels were subsequently used as crystallization media to obtain lysozyme (Lzm) crystals. Composite Lzm@MNP crystals were later cross-linked at different degrees to control their dissolution rate.

Herein, we present a proof of concept of a novel active compounds’ delivery vehicle, in which the vehicle and itscargo have an active and remedial role.