A "live in situ reassembly" treatment strategy for bacterial infection

【introduction】

Nanomaterials and nanotechnology have received the attention of the scientific community in recent years, and their applications in various fields are becoming more and more extensive. Due to the special size effect of nanomaterials, the application of nanoparticles, nanotubes and various nanotechnology in biomedicine is booming and full of momentum. To date, many nanosystems have been developed as antibiotic alternatives for the treatment of bacterial infections. However, these advanced systems are limited due to their non-target aggregation and subsequent side effects.

[Introduction]

Recently, Dr. Wang Hao from the National Nanoscience Center and Associate Research Fellow Qiao Zengying (co-author) and others demonstrated pathologically-driven self-assembled nanostructures, which showed super accumulation at the target position due to the assembly-induced retention (AIR) effect. Retention ability. Inspired by this effect, this paper discusses a new antibacterial strategy—the “in-situ reassembly” strategy. With the aid of enzymes, the antibacterial active nanoparticles transform from spherical to fibrous structures, thus simultaneously in the bacterial infection site. Achieve long-term accumulation and enhance the efficacy of antibacterial. Related results are published in Adv. Mater. entitled "An "On-Site Transformation" Strategy for Treatment of Bacterial Infection".

[Graphic introduction]

Fig.1 Schematic diagram of self-assembly of CPC and principle of enzyme-induced morphological transformation

a) i) self-assembly of CPC into nanoparticles containing PEG shell; ii) cleavage of degradable peptide in the presence of gelatinase to strip the protective shell; iii) destruction of hydrophobic/hydrophilic equilibrium leading to chitosan Hydrogen bond interaction of the chain, spontaneously promotes self-assembly and reorganization of the fiber structure;

b) i) In the infective microenvironment, the CPC nanoparticles accumulated at the site of infection are cleaved by gelatinase produced by gelatinase-positive bacteria, causing in situ morphological transformation; ii) fibrous nanostructures are in situ in infected tissue Produced to allow nanomaterials to accumulate and their retention time to be extended; iii) Nanofibers with exposed antimicrobial peptides exhibit high antibacterial ability.

Figure 2 Variability characteristics of CPC-1


a) Schematic diagram of morphological transformation of CPC-1 under enzyme induction;

b) representative TEM image of each time period after immersing CPC-1 nanoparticles in gelatinase (10 μg/mL) tris buffer (pH 7.4) for a period of time; scale bar, 100 nm;

c) CD spectra of chitosan (0.5 mg/mL), KLAK peptide and fiber CPC-3 (100 x 10-6 M, based on KLAK) in PB solution (10 x 10-3 M, pH 7.4).

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