A Perspective on the Trends and Challenges Facing Porphyrin‐Based Anti‐Microbial Materials

Abstract

The emergence of multidrug resistant bacterium threatens to unravel global healthcare systems, built up over centuries of medical research and development. Current antibiotics have little resistance against this onslaught as bacterium strains can quickly evolve effective defense mechanisms. Fortunately, alternative therapies exist and, at the forefront of research lays the photodynamic inhibition approach mediated by porphyrin based photosensitizers. This review will focus on the development of various porphyrins compounds and their incorporation as small molecules, into polymers, fibers and thin films as practical therapeutic agents, utilizing photodynamic therapy to inhibit a wide spectrum of bacterium. The use of photodynamic therapy of these porphyrin molecules are discussed and evaluated according to their electronic and bulk material effect on different bacterium strains. This review also provides an insight into the general direction and challenges facing porphyrins and derivatives as full-fledged therapeutic agents and what needs to be further done in order to be bestowed their rightful and equal status in modern medicine, similar to the very first antibiotic; penicillin itself. It is hoped that, with this perspective, new paradigms and strategies in the application of porphyrins and derivatives will progressively flourish and lead to advances against disease.

Cholesterol-Assisted Bacterial Cell Surface Engineering for Photodynamic Inactivation of Gram-Positive and Gram-Negative Bacteria

“…To isolate RBCs, blood was centrifuged three times and re-suspended in a PBS 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 12 be degraded in human body and may cause severe side effects. 4 In comparison, porphyrin-based PS molecules have excellent biocompatibility and good therapeutic efficacy. 61−63 Specifically, protoporphyrin naturally occurs in human hemoglobin, which reduces the possibilities of systemic toxicity as well as allergic reaction.…”

“…61−63 Specifically, protoporphyrin naturally occurs in human hemoglobin, which reduces the possibilities of systemic toxicity as well as allergic reaction. 4 In our design, protoporphyrin-derived PpIX was selected as the antibacterial PS. However, anionic PpIX can only photoinactivate Gram-positive bacteria with limited efficiency.…”

“…4 The highly oxidative 1 O 2 can cause irreversible damage to many important biomolecules such as membrane lipids, 5 proteins, 6 and cellular DNAs, 7 which ultimately leads to bacterial cell death. In addition, MDR bacteria have shown to be as vulnerable as non-MDR bacteria to PDT, 8,9 which offers tremendous promise for PDT to combat drug resistance.…”

“…8,10 This highly organized membrane structure of Gram-negative bacteria acts as a formidable defensive barrier to numerous drug molecules. 4 To solve this problem, one approach is to use outer membrane-disrupting agents, such as the 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 4 lipopeptide antibiotic polymixin B 11 and ethylenediaminetetraacetic acid (EDTA), 12 to increase the susceptibility of bacteria to PDT. However, the adoption of such pretreatment may raise concerns regarding the potential toxicity and tissue reaction of these agents.…”

Latest Advances in Antibacterial Materials

“…70,71 Polymers which incorporate various biocides including heavy metals, antibiotics, cationic molecules, antimicrobial peptides and enzymes into the polymeric systems have been developed. 72 Subsequently, these bactericidal components will be either released to kill surrounding bacteria or immobilized on the polymer¯lm surface to kill bacteria upon contact. Silver is the most commonly used heavy metal for antibacterial materials.…”