Mechanistics and photo‐energetics of macrocycles and photodynamic therapy: An overview of aspects to consider for research

Abstract

Research within the field of photodynamic therapy has escalated over the past 20 years. The required conjunctional use of photosensitizers, particularly of the macrocycle structure, has lead to a vast repertoire of derivatives that branch classes and subclasses thereof. Each exhibits a differential range of physiochemical properties that influence their potential applications within the larger phototherapy field for use in either diagnostics, photodynamic therapy, both or none. Herein, we provide an overview of these properties as they relate to photodynamic therapy and to a lesser extent diagnostics. By summarizing the mechanistics of photodynamic therapy coupled to the photo-energetics displayed by macrocycle photosensitizers, we aimed to highlight the critical aspects any researcher should be aware of and consider when selecting and performing research for therapeutic application purposes. These include photosensitizer, photophysical and structural properties, synthesis design and subsequent attributes, main applications within research, common shortcomings exhibited and the current methods practiced to overcome them. K E Y W O R D Sco

Macrocycles, the edge of drug‐likeness chemical space or Goldilocks zone?

“…The review by Horne and Cronjé discusses mechanistic aspects of photosensitizer design and the wider photosensitizer classes and also goes into detail on some of the shortcomings and difficulties of formulation of such lipophilic structures. Liposomes, cyclodextrins and lipoproteins are all discussed as formulation aids.…”

Cyanoarylporphyrazines with High Viscosity Sensitivity: A Step towards Dosimetry-Assisted Photodynamic Cancer Treatment

“…The excited photosensitizer reacts with cellular oxygen, resulting in the generation of cytotoxic reactive oxygen species (e.g., singlet oxygen ( 1 O 2 ), superoxide anion (O 2 −• ), hydroperoxide radical (HOO • ), peroxides (H 2 O 2 , ROOH), and hydroxyl radical (HO • )), and initiating molecular mechanisms which lead to tumor tissue destruction and vascular damage [ 1 , 2 , 3 ]. The efficient development of photodynamic reaction depends primarily on the photophysical and photochemical properties of the photosensitizer [ 4 , 5 , 6 ], its tissue distribution [ 7 , 8 ], its uptake by cancer cells and subcellular localization [ 4 , 9 , 10 , 11 ], and the irradiation dose [ 12 , 13 ].…”

Porphyrin‐Based Metal−Organic Framework Compounds as Promising Nanomedicines in Photodynamic Therapy

“…[11] Type II PDT is the most common PDT. [12] However, how to effectively improve the efficacy of PDT and enhance the concentration of photosensitizers during finding tumors while reducing toxic side effects on healthy cells is an urgent problem to be solved. [13] For PDT, choosing the right photosensitizer is crucial.…”