Abstract
Photodynamic inactivation of microorganisms has gained substantial attention due to its unique mode of action, in which pathogens are unable to generate resistance, and due to the fact that it can be applied in a minimally invasive manner. In photodynamic therapy (PDT), a non-toxic photosensitizer (PS) is activated by a specific wavelength of light and generates highly cytotoxic reactive oxygen species (ROS) such as superoxide (O2−, type-I mechanism) or singlet oxygen (1O2*, type-II mechanism). Although it offers many advantages over conventional treatment methods, ROS-mediated microbial killing is often faced with the issues of accessibility, poor selectivity and off-target damage. Thus, several strategies have been employed to develop target-specific antimicrobial PDT (aPDT). This includes conjugation of known PS building-blocks to either non-specific cationic moieties or target-specific antibiotics and antimicrobial peptides, or combining them with targeting nanomaterials. In this review, we summarise these general strategies and related challenges, and highlight recent developments in targeted aPDT.
Highlights
The revolutionary discovery and mass production of penicillin in the first half of the 20th century opened a new era in the fight against bacterial infections [1,2], and the development of new antibiotics in the following decades reduced considerably the mortality caused by infectious diseases
Positively charged PS appear promising for antimicrobial PDT (aPDT) as they can interact electrostatically with the negatively charged bacterial membrane, and the synthesis of several PS functionalised with small cationic functional groups has been reported [31,32,33,34,35]
The correct selection of a targeting moiety to combine with an aPDT dye is the first step in this direction
Summary
The revolutionary discovery and mass production of penicillin in the first half of the 20th century opened a new era in the fight against bacterial infections [1,2], and the development of new antibiotics in the following decades reduced considerably the mortality caused by infectious diseases. Following the major concerns around MDR bacteria, several new PS have been tested, adapted or developed for aPDT [30] In this sense, positively charged PS appear promising for aPDT as they can interact electrostatically with the negatively charged bacterial membrane, and the synthesis of several PS functionalised with small cationic functional groups has been reported [31,32,33,34,35]. While Gram+ bacteria are the cause of serious infectious diseases, more than 90% of Gram− bacteria are considered pathogenic, and since their membrane composition is such that many antibacterial agents fail to enter (vide infra), they represent a major threat Because of these selectivity issues and potential side-effects, and in contrast to the use of PDT in oncology, aPDT has yet to translate widely into clinics [36,37,38,39,40]. We stress that the focus here is on the photodynamic treatment of infectious diseases, but invite the reader to explore other key applications such as self-disinfecting materials and fabrics [45,46]
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