A dynamic covalent polymeric antimicrobial for conquering drug‐resistant bacterial infection

Abstract

Increasing bacterial drug resistance to antibiotics has posed a major threat to contemporary public health, which resulted in a large number of people suffering from serious infections and ending up dying without any effective therapies every year. Here, a dynamic covalent polymeric antimicrobial, based on phenylboronic acid (PBA)installed micellar nanocarriers incorporating clinical vancomycin and curcumin, is developed to overcome drug-resistant bacterial infections. The formation of this antimicrobial is facilitated by reversible dynamic covalent interactions between PBA moieties in polymeric micelles and diols in vancomycin, which impart favorable stability in blood circulation and excellent acid-responsiveness in the infection microenvironment. Moreover, the structurally similar aromatic vancomycin and curcumin molecules can afford π-π stacking interaction to realize simultaneous delivery and release of payloads. In comparison with monotherapy, this dynamic covalent polymeric antimicrobial demonstrated more significant eradication of drug-resistant bacteria in vitro and in vivo due to the synergism of the two drugs. Furthermore, the achieved combination therapy shows satisfied biocompatibility without unwanted toxicity. Considering various antibiotics contain diol and aromatic structures, this simple and robust strategy can become a universal platform to combat the ever-threatening drug-resistant infectious diseases.

A Membrane Curvature Modulated Lipopeptide to Broadly Combat Multidrug-Resistant Bacterial Pneumonia with Low Resistance Risk

“…2 It is worrying that the emergence of multidrug-resistant (MDR) Gram-negative bacteria 3 in ESKAPE 4 has posed serious health impacts to human beings. 5 Recently, the World Health Organization (WHO) reported that the rate of resistance to ciprofloxacin (Cip) varied from 8.4% to 92.9% for Escherichia coli and from 4.1% to 79.4% for Klebsiella pneumoniae. 6 It is estimated by WHO that the improper use of antibiotics during the COVID-19 pandemic will further exacerbate this trend, and hence overcoming the drug resistance of Gram-negative bacteria can become a major global security challenge in the near future.…”

“…Antimicrobial resistance (AMR) is an ever-increasing public threat to global health, and it has caused at least 700 000 deaths . It is worrying that the emergence of multidrug-resistant (MDR) Gram-negative bacteria in ESKAPE has posed serious health impacts to human beings . Recently, the World Health Organization (WHO) reported that the rate of resistance to ciprofloxacin (Cip) varied from 8.4% to 92.9% for Escherichia coli and from 4.1% to 79.4% for Klebsiella pneumoniae .…”

Dual-targeted poly(amino acid) nanoparticles deliver drug combinations on-site: an intracellular synergistic strategy to eliminate intracellular bacteria

“…Their similar release behaviors were mainly due to the p-p stacking interaction between Van and Cur. 52 This long-term, sustainable and stable multi-drug release is essential for the long-term inhibition of intracellular bacterial growth. 53,54 In addition, TEM images showed that (Van 1.5 + Cur 3.0 )@F(AM) NPs were homogeneous spherical particles with an average diameter of 357 nm (Fig.…”

Synergistic Poly(lactic acid) Antibacterial Surface Combining Superhydrophobicity for Antiadhesion and Chlorophyll for Photodynamic Therapy

“…Cumulative evidence demonstrated that some aromatic photosensitizers [e.g., chlorophyll (Chl) and curcumin] are natural antibacterial compounds extracted from plants with low toxicity. They have been proved to possess broad bactericidal activity against not only Gram-positive but also Gram-negative bacteria via interacting with cellular components of bacteria. , Chl is a natural photosensitizer for PDT with the advantages of excellent ROS yield and good biocompatibility . To overcome the dilemmas include antibacterial adhesion and bactericidal strategies, both have limitations and most porphyrin-based photosensitizers have toxicity, thus a synergistic antibacterial surface consisting of both superhydrophobic and PDT characteristics would be an interesting strategy to inactivate bacteria without triggering drug resistance and effectively inhibit bacterial infection.…”