Biomineralized Cascade Enzyme-Encapsulated ZIF-8 Nanoparticles Combined with Antisense Oligonucleotides for Drug-Resistant Bacteria Treatment

Abstract

The unrestrained use of antibiotics accelerates the development of drug-resistant bacteria and leads to an increasing threat to human health. Therefore, there is an urgent need to explore novel and effective strategies for the treatment of bacterial infections. Herein, zeolite imidazole framework-8 (ZIF-8) material was utilized to construct biomineralized nanomaterial (GOx&HRP@ZIF-8/ASO) by encapsulating biological cascade enzymes and combining with antisense oligonucleotides (ASOs), which achieved effective and synergistic antidrug-resistant bacteria therapy. Various in vitro assays confirmed that GOx&HRP@ZIF-8/ASO exhibited excellent antibacterial properties against Escherichia coli, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA) during catalysis of glucose (Glu), especially the minimum inhibitory concentration (MIC) against MRSA was only 16 μg/mL. Compared with simple ZIF-8 (32.85%) and ftsZ ASO (58.65%), GOx&HRP@ZIF-8/ASO+Glu exhibited superb biofilm destruction ability, and the bacteria removal efficiency of the MRSA biofilm could be as high as 88.2%, indicating that the reactive oxygen species (ROS) produced by the cascade enzyme reaction imparted the main synergistic antibacterial capability, and simultaneously, ftsZ ASO significantly enhanced the antibacterial effect by inhibiting the expression of the ftsZ gene. In vivo anti-infection treatment experiments revealed that GOx&HRP@ZIF-8/ASO exhibited the best wound repairing performance and excellent biocompatibility in the presence of Glu. These findings suggested that GOx&HRP@ZIF-8/ASO has favorably realized high-efficiency treatment of MRSA infection and filled the gap in the antibacterial application of biological enzymes.

Porous organic polymers for drug delivery: hierarchical pore structures, variable morphologies, and biological properties

“…Compared with MOFs, which are frequently used as DDS, [177][178][179][180][181][182][183] POP-based DDS are more safe. In particular, because of their metal components, MOFs can be toxic or have low biocompatibility.…”

Designed Synthesis of Compartmented Bienzyme Biocatalysts Based on Core–Shell Zeolitic Imidazole Framework Nanostructures

“…Ren et al [28] encapsulated carbonic anhydrase, formate dehydrogenase, cofactor (NADH), and glutamate dehydrogenase into a single ZIF-8 crystal to construct a nanoscale multienzyme reactor for the conversion of carbon dioxide to formate. Similarly, Zhang et al [29] constructed biomineralized nanomaterials by the co-immobilization of cascade enzymes and antisense oligodeoxynucleotides within ZIF-8, which had a good biofilm destruction ability. Wu et al [24] co-immobilized glucose oxidase and horseradish peroxidase (GOx and HRP) into a single ZIF-8 particle using a one-step method to synthesize GOx/HRP@ZIF-8 as efficient glucose biosensors.…”

“…Similarly, Zhang et al. [ 29 ] constructed biomineralized nanomaterials by the co‐immobilization of cascade enzymes and antisense oligodeoxynucleotides within ZIF‐8, which had a good biofilm destruction ability. Wu et al.…”

Double-Edged Nanobiotic Platform with Protean Functionality: Leveraging the Synergistic Antibacterial Activity of a Food-Grade Peptide to Mitigate Multidrug-Resistant Bacterial Pathogens

“…However, indiscriminate use and a dearth of novel therapeutics entering the antibiotic pipeline have led to an escalation of the crisis of antibiotic-resistant pathogens, ushering us into the imminent postantibiotic era. , The present pandemic associated with the use of massive amounts of antimicrobials and sanitizers is likely to escalate the next pandemic of antibiotic-resistant pathogens. , The resistance of pathogenic bacteria to drugs is mainly attributed to evolving multiple strategies to either efflux or inactivate the antibiotics, the formation of biofilms, and turning into persisters. , A recent report estimated that, in addition to an economic loss of US $100 trillion, antibiotic-resistant infections are expected to kill 10 million people each year by 2050 . Myriad efforts have been dedicated to the battle against resistant infections, leading to the development of new antibacterial materials which differ in mode of action from antibiotics. − Antimicrobial peptides (AMPs) represent one such category which has been advocated as potential therapeutic alternative to antibiotics . The fact that these molecular knives act by inflicting severe damage to bacterial cell walls makes it difficult for the pathogen to evolve and acquire resistance against AMPs.…”