Synthesis of Photosensitizers Based on Tetrapyrrolic Macrocycles for Combination with Antibiotics: Dual Inactivation of Bacteria

Abstract

The combination of photodynamic therapy with antibiotics or antimicrobial peptides for inactivation of bacteria is an area of growing interest due to the synergistic effect already observed by many authors. It has been shown that the efficiency of this dual antimicrobial therapy is highly dependent on the structure of the photosensitizer, being tetrapyrrolic macrocycles the ones with most promising results. There are a few review articles in the recent literature describing the main microbiological results concerning this dual inactivation of bacteria, but none of them focus on the synthetic processes of these photosensitizers and their remarkable chemical versatility. Therefore, herein we present an overview on synthetic methodologies for preparation of tetrapyrrolic macrocycles and their conjugates with antibiotics or antimicrobial peptides, for use in dual inactivation of bacteria. This review will be divided in two sections concerning the physical or covalent combinations of PS with antibiotic/cationic peptides, followed by brief critical analysis on their corresponding antimicrobial outcomes.

Antimicrobial Photodynamic Therapy for the Remote Eradication of Bacteria

“…Indeed, the rise in multi‐drug resistant (MDR) bacteria strains have become a serious public health concern globally. As such, these strains could lead humanity into the “dark ages” whereby antibiotics fail to be effective in fighting bacterial infections [105] . In this sub‐section, we will be providing an overview of some of the antibiotic‐resistant strains, and how did the bacteria strains develop resistance their respective antibiotics.…”

FRET‐Amplified Singlet Oxygen Generation by Nanocomposites Comprising Ternary AgInS2/ZnS Quantum Dots and Molecular Photosensitizers

“…Antibacterial photodynamic therapy (a‐PDT) is a promising non‐invasive treatment modality that utilizes the combination of a light‐activated photosensitizer, molecular oxygen, and appropriate excitation sources to generate reactive oxygen species (ROS), such as singlet oxygen (SO), superoxide anion, and hydroxyl radical, [3] which can oxidatively destroy pathogenic bacteria [4–6] . For the past several years, conventional tetrapyrrole‐based photosensitizers, which have a high molar extinction coefficient and strong ability to generate ROS, have been widely employed in a‐PDT [7–12] . However, the effective use of these therapeutic agents is significantly limited by a number of their shortcomings, namely poor water solubility, rapid photobleaching, and low selectivity of tissue accumulation [13,14] .…”

“…[4][5][6] For the past several years, conventional tetrapyrrole-based photosensitizers, which have a high molar extinction coefficient and strong ability to generate ROS, have been widely employed in a-PDT. [7][8][9][10][11][12] However, the effective use of these therapeutic agents is significantly limited by a number of their shortcomings, namely poor water solubility, rapid photobleaching, and low selectivity of tissue accumulation. [13,14] In this regard, the development of novel biocompatible drug systems for a-PDT, which can overcome the limitations of conventional photosensitizers and significantly increase the efficiency of ROS generation, has become a pressing issue.…”

Photodynamic inactivation of E. coli with cationic imidazolyl-porphyrin photosensitizers and their synergic combination with antimicrobial cinnamaldehyde

“…Recent studies emphasized that the synergic combination of PDI with existing antibiotics is a more promising approach to tackle multi-resistant bacteria and delay antibiotic resistance [26,33,34]. This approach enhances the efficacy of antibacterial treatments by leveraging the strengths of both PDI and antibiotics [27,[35][36][37]. We showed [26], in agreement with literature [34,36], that the order and number of each individual treatment sessions impact the inactivation of MRSA or E. coli, and found that PDI followed by antibiotic administration yielded the best results.…”