Recent Progress in the Characterization, Synthesis, Delivery Procedures, Treatment Strategies, and Precision of Antimicrobial Peptides

Abstract

Infectious diseases are constantly evolving to bypass antibiotics or create resistance against them. There is a piercing alarm for the need to improve the design of new effective antimicrobial agents such as antimicrobial peptides which are less prone to resistance and possess high sensitivity. This would guard public health in combating and overcoming stubborn pathogens and mitigate incurable diseases; however, the emergence of antimicrobial peptides' shortcomings ranging from untimely degradation by enzymes to difficulty in the design against specific targets is a major bottleneck in achieving these objectives. This review is aimed at highlighting the recent progress in antimicrobial peptide development in the area of nanotechnology-based delivery, selectivity indices, synthesis and characterization, their doping and coating, and the shortfall of these approaches. This review will raise awareness of antimicrobial peptides as prospective therapeutic agents in the medical and pharmaceutical industries, such as the sensitive treatment of diseases and their utilization. The knowledge from this development would guide the future design of these novel peptides and allow the development of highly specific, sensitive, and accurate antimicrobial peptides to initiate treatment regimens in patients to enable them to have accommodating lifestyles.

Keywords: antimicrobial peptides; broad-spectrum; characterization; coating; doping; synthesis.

Figure 1

The anti-inflammatory mechanism of CXCL14-C17 on various antibiotic-resistant bacteria. Rajasekaran et al., (2019) [80], recorded that in lipopolysaccharide (LPS)-stimulated RAW264.7 cells the release of “bacterial LPS” instigated an induction of proinflammatory genes, such as the genes associated with nitric oxide (NO) production, tumor necrosis factor (TNF)-α, interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1. This induction of proinflammatory genes resulted in the overproduction of proinflammatory cytokinins ultimately leading to the sepsis of the RAW264.7 cells. However, the authors likewise depicted that with the presence of CXCL14-C17 AMP, in conjunction with the antimicrobial properties, these AMPs possess on bacteria (methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Pseudomonas aeruginosa (MDRPA), and vancomycin-resistant Enterococcus faecium (VREF)), the induction of proinflammatory genes was blocked, reducing the occurrence of sepsis. Thus, CXCL14-C17 illustrated both antimicrobial and anti-inflammatory properties against invading microbial infections.

Figure 2

Representation of the molecular mechanisms of NRC-03-induced apoptosis and cell death in oral squamous cell carcinoma (OSCC) cells. The cationic nature of NRC-03 grants this cationic AMP to purposefully target negatively charged cancer cells, such as OSCC. NRC-03 easily enters the cancerous cells and has three main targets within these cells. They were shown to be bound to the cell membrane, nucleus, and mitochondria. Two pathways thus ensue wherein the cell death/apoptotic pathway NRC-03 bound to the nucleus results in DNA fragmentation while the cell-membrane-bound NRC-03 has been shown to increase the prevalence of blebbing. More importantly, Hou et al., (2022) [143], noted that NRC-03-induced expression of CypD has been shown to cause the prolonged opening of the mPTP channel, which leads to the increased efflux of calcium (Ca²⁺) and Reactive Oxygen Species (ROS) into the cytosol. This prolonged CypD-dependent opening of the mPTP channel thus caused mitochondrial dysfunction, swelling, and rupture, supplementing cell death in the OSCC cells. Hence, Hou et al., (2022) [143], stated that the molecular mechanism of NRC-03-induced cell death is mainly caused by the mitochondrial oxidative stress-mediated altered mitochondrial function.