Remarkable enhancement of cinnamaldehyde antimicrobial activity encapsulated in capped mesoporous nanoparticles: A new "nanokiller" approach in the era of antimicrobial resistance

[EN] Combating antimicrobial resistance is one of the biggest health challenges because of the ineffectiveness of standard biocide treatments. This challenge could be approached using natural products, which have demonstrated powerful therapeutics against multidrug-resistant microbes. In the present work, a nanodevice consisting of mesoporous silica nanoparticles loaded with an essential oil component (cinnamaldehyde) and functionalized with the polypeptide epsilon-poly- L -lysine is developed and used as an antimicrobial agent. In the presence of the corresponding stimuli (i.e., exogenous proteolytic enzymes from bacteria or fungi), the polypeptide is hydrolyzed, and the cinnamaldehyde delivery is enhanced. The nanodevice's release mechanism and efficacy are evaluated in vitro against the pathogenic microorganisms Escherichia coli , Staphylococcus aureus , and Candida albicans . The results demonstrate that the new device increases the delivery of the cinnamaldehyde via a biocontrolled uncapping mechanism triggered by proteolytic enzymes. Moreover, the nanodevice notably improves the antimicrobial efficacy of cinnamaldehyde when compared to the free compound, ca. 52-fold for E. coli , ca. 60fold for S. aureus , and ca. 7-fold for C. albicans . The enhancement of the antimicrobial activity of the essential oil component is attributed to the decrease of its volatility due to its encapsulation in the porous silica matrix and the increase of its local concentration when released due to the presence of microorganisms. This research was supported by projects PID2021-126304OB-C41 and PID2021-128141OB-C22 funded by MCIN/AEI/10.13039/501100011033/and by European Regional Development Fund-A way of doing Europe. This study was also supported by Generalitat Valenciana (CIPROM/2021/007) . This research was supported by CIBER-Consorcio Centro de Investigacion Biomedica en Red- (CB06/01/2012) , Instituto de Salud Carlos III, Ministerio de Ciencia e Innovacion. This work was also funded by the Generalitat Valenciana and Agencia Valenciana de la Innovacion (MCIN) (INNEST/2021/169 project) and is susceptible to be co-founded by the European Union. A. M.-A. thanks to the Universitat Politecnica de Valencia (UPV) for her Ph.D. grant (DOCEMPR22) . A.B. thanks the MCIN for her BG20/00020 contract and her PAID-PD-22 project funded by UPV. Morella-Aucejo, Á.; Medaglia, S.; Ruiz Rico, M.; Martínez-Máñez, R.; Marcos Martínez, MD.; Bernardos Bau, A. (2024). Remarkabl