Design features for optimization of tetrapyrrole macrocycles as antimicrobial and anticancer photosensitizers

Abstract

Photodynamic therapy (PDT) uses non-toxic dyes called photosensitizers (PS) and harmless visible light that combine to form highly-toxic reactive oxygen species that kill cells. Originally a cancer therapy, PDT now includes applications for infections. The most widely studied PS are tetrapyrrole macrocycles including porphyrins, chlorins, bacteriochlorins and phthalocyanines. The present review covers the design features in PS that can work together to maximize the PDT activity for various disease targets. Photophysical and photochemical properties include the wavelength and size of the long-wavelength absorption peak (for good light penetration into tissue), the triplet quantum yield and lifetime, and the propensity to undergo Type I (electron-transfer) or Type II (energy-transfer) photochemical mechanisms. The central metal in the tetrapyrrole macrocycle has a strong influence on the PDT activity. Hydrophobicity and charge are important factors that govern interactions with various types of cells (cancer and microbial) in vitro, and the pharmacokinetics and biodistribution in vivo. Hydrophobic structures tend to be water-insoluble and require a drug delivery vehicle for maximal activity. Molecular asymmetry and amphiphilicity are also important for high activity. In vivo some structures possess the ability to selectively accumulate in tumors, and to localize in the tumor microvasculature producing vascular shutdown after illumination.

Xanthene Dyes and Green LED for the Inactivation of Foodborne Pathogens in Planktonic and Biofilm States

“…Another point that may be considered regarding the different susceptibility between Gram-positive and Gram-negative bacteria is the charge features of the PS agent. It is well established that cationic PSs present better antimicrobial efficiency compared to the neutral/anionic ones (39) since they are likely to bind to the negatively charged surface of Gram-negative bacteria (40). Considering that the xanthenes used in the present study are in dianionic form (pH 7.4), it may be hypothesized that the presence of negative charges could reduce the interaction with Gram-negative microorganisms.…”

Amphiphilic tetracationic porphyrins are exceptionally active antimicrobial photosensitizers: In vitro and in vivo studies with the free‐base and Pd‐chelate

“…Some factors that influence the structure‐function relationships of antimicrobial photosensitizers are beginning to emerge . It is well known that the presence of cationic charges is needed for activity against Gram‐negative bacteria .…”

Proton‐Dependent Switching of a Novel Amino Chlorin Derivative as a Fluorescent Probe and Photosensitizer for Acidic Media

“…[51] However,i t should be noted that most PDI studies have been conducted at physiological pH, and to the best of our knowledge there have been no studies concerning actual applicationso fc hlorins as antimicrobialp hotosensitizers in acid media. [6,9] This can be explained by taking into accountt hat most tetrapyrrolic macrocycles do not have suitable characteristics for use in PDI at low pH, since their inner Na toms can be protonated, leading to loss of the appropriate spectroscopic and photodynamic features. TPCF 20 -NMe 2 remainsi nactive at neutralp Ha nd the photoinactivation capacity can be efficiently switched on in acidic mediatoe radicate bacteria.…”

“…[7,8] In addition, chlorins have also been proposed as photosensitizers with potentiala pplicationsi np hotodynamic inactivation( PDI) of microorganisms. [9] This approach is based on the accumulationo faphotosensitizer in microbial cells. [10] Irra-diation with visible light excites the photosensitizer,w hich induces the formation of ROS under aerobiosis.…”