Effective delivery of the anti-mycobacterial peptide NZX in mesoporous silica nanoparticles

Abstract

Background Intracellular delivery of antimicrobial agents by nanoparticles, such as mesoporous silica particles (MSPs), offers an interesting strategy to treat intracellular infections. In tuberculosis (TB), Mycobacterium tuberculosis avoids components of the immune system by residing primarily inside alveolar macrophages, which are the desired target for TB therapy. Methods and findings We have previously identified a peptide, called NZX, capable of inhibiting both clinical and multi-drug resistant strains of M . tuberculosis at therapeutic concentrations. In this study we analysed the potential of MSPs containing NZX for the treatment of tuberculosis. The MSPs released functional NZX gradually into simulated lung fluid and the peptide filled MSPs were easily taken up by primary macrophages. In an intracellular infection model, the peptide containing particles showed increased mycobacterial killing compared to free peptide. The therapeutic potential of peptide containing MSPs was investigated in a murine infection model, showing that MSPs preserved the effect to eliminate M . tuberculosis in vivo . Conclusions In this study we found that loading the antimicrobial peptide NZX into MSPs increased the inhibition of intracellular mycobacteria in primary macrophages and preserved the ability to eliminate M . tuberculosis in vivo in a murine model. Our studies provide evidence for the feasibility of using MSPs for treatment of tuberculosis.

Unbiased Identification of Angiogenin as an Endogenous Antimicrobial Protein With Activity Against Virulent Mycobacterium tuberculosis

“…Another promising delivery platform are mesoporous nanoparticles, which have been used to deliver antimicrobial peptides, such as NZX and LL-37 ( Braun et al, 2016 ; Tenland et al, 2019 ) to enhance protection against tuberculosis in mice ( Tenland et al, 2019 ). Nanoparticles also promote stability, bioavailability, and efficacy of conventional antituberculotic drugs ( Clemens et al, 2012 ; Singh, 2019 ).…”

Nano-Based Drug Delivery or Targeting to Eradicate Bacteria for Infection Mitigation: A Review of Recent Advances

“…NZX is an antimicrobial peptide capable of suppressing the growth of drug-resistant M. tuberculosis. Tenland et al (2019) aimed to entrap NZX into MSNs for treating tuberculosis because of the large uptake of MSNs by macrophages. The nanoparticles presented increased intra-macrophage bacteria killing compared to free NZX.…”

Silica Nanoparticles—A Versatile Tool for the Treatment of Bacterial Infections

“…Hence, an efficient nanocarrier like MSN is vital to execute the delivery of peptides to the target site. In a recent study, Tenland and team loaded an effective anti-TB peptide, called NZX into mesoporous silica nanoparticles to improve its delivery efficacy (Tenland et al, 2019 ). In vivo studies suggested that NZX-loaded mesoporous silica nanoparticles were able to significantly reduce the bacterial load compared to the RIF treatment.…”