Virus-inspired surface-nanoengineered antimicrobial liposome: A potential system to simultaneously achieve high activity and selectivity

Abstract

Enveloped viruses such as SARS-CoV-2 frequently have a highly infectious nature and are considered effective natural delivery systems exhibiting high efficiency and specificity. Since simultaneously enhancing the activity and selectivity of lipopeptides is a seemingly unsolvable problem for conventional chemistry and pharmaceutical approaches, we present a biomimetic strategy to construct lipopeptide-based mimics of viral architectures and infections to enhance their antimicrobial efficacy while avoiding side effects. Herein, a surface-nanoengineered antimicrobial liposome (SNAL) is developed with the morphological features of enveloped viruses, including a moderate size range, lipid-based membrane structure, and highly lipopeptide-enriched bilayer surface. The SNAL possesses virus-like infection to bacterial cells, which can mediate high-efficiency and high-selectivity bacteria binding, rapidly attack and invade bacteria via plasma membrane fusion pathway, and induce a local “burst” release of lipopeptide to produce irreversible damage of cell membrane. Remarkably, viral mimics are effective against multiple pathogens with low minimum inhibitory concentrations (1.6–6.3 μg mL −1 ), high bactericidal efficiency of >99% within 2 h, >10-fold enhanced selectivity over free lipopeptide, 99.8% reduction in skin MRSA load after a single treatment, and negligible toxicity. This bioinspired design has significant potential to enhance the therapeutic efficacy of lipopeptides and may create new opportunities for designing next-generation antimicrobials.

Membrane-disruptive peptides/peptidomimetics-based therapeutics: Promising systems to combat bacteria and cancer in the drug-resistant era

“…In another application, Wu's group 207 presented a biomimetic strategy to construct virus-inspired, surface-nanoengineered antimicrobial liposomes, simultaneously achieving enhanced antimicrobial activity and selectivity of lipopeptides ( Fig. 11 A).…”

“…In addition to the four main administration routes aforementioned, MDP-based delivery systems have also been proposed for subcutaneous 207 , nasal 364 , 365 , ocular 366 , 367 and intratumoral 368 applications, which are worthy of consideration for further investigation and development. While MDPs and their formulations have been extensively investigated in antimicrobial applications, their antitumor applications are still in infancy and rarely studied.…”

Macromolecular Nanotherapeutics and Antibiotic Adjuvants to Tackle Bacterial and Fungal Infections

“…[ 26,69 ] In the recent past, significant efforts have already been directed to develop several AMP‐mimicking synthetic antimicrobial polymers along with numerous small molecular peptidomimetics. [ 70–77 ] The low‐cost synthesis, ability to easily modulate the structural parameters, potent antimicrobial activity, and stability has made them advantageous over the other synthetic analogues of AMPs. Researchers throughout the world have developed numerous polymeric architecture including random copolymers, block copolymers, homopolymers, zwitterionic, and branched polymers with different polymeric backbone, such as polynorbornenes/oxanorbornenes ( Figure 2 A), [ 78–84 ] polymethacrylate/polyacrylates (Figure 2B), [ 85–91 ] poly‐ β −lactam (Figure 2C), [ 92–95 ] polymaleimides (Figure 2D), [ 95–100 ] glycosylated cationic block co‐beta‐peptides (Figure 2E), [ 101 ] polycarbonates (Figure 2F), [ 102–107 ] polyamides, [ 108 ] poly(benzyl ether)s, [ 109 ] polyionenes, [ 110,111 ] poly(2‐oxazoline), [ 112,113 ] and many other polymeric amphiphiles (Figure 2).…”

Formulation of pH-responsive PEGylated nanoparticles with high drug loading capacity and programmable drug release for enhanced antibacterial activity

“…Novel drug delivery system, because of its subcellular morphology, dimension, biocompatibility, biodegradability and surface area, has showcased their importance and efficiency in resolving the disadvantages of conventional antibiotics via improving the drug delivery and keeping high drug concentration at targeted bacterial infection sites [ [11] , [12] , [13] , [14] , [15] , [16] , [17] ]. Recently, responsive drug delivery has great potential in specific treatments by lowering the side effects and improving the efficacy.…”