New Approaches to Photodynamic Therapy from Types I, II and III to Type IV Using One or More Photons

Abstract

Photodynamic therapy (PDT) is an alternative cancer treatment to conventional surgery, radiotherapy and chemotherapy. It is based on activating a drug with light that triggers the generation of cytotoxic species that promote tumour cell killing. At present, PDT is mainly used in the treatment of wet age-related macular degeneration, for precancerous conditions of the skin (e.g. actinic keratosis) and in the palliative care of advanced cancers, for instance of the bladder or the oesophagus. Due to a lack of phase III clinical trials and limitations of light penetration to deeper lying tumours (in excess of 1 cm), PDT is still not used as a first line cancer treatment, which is surprising given the first clinical trials by Dougherty's group dating back to the 1970's. However research continues to demonstrate the potential benefits of PDT and the need to stimulate funding and uptake of clinical studies using next generation photosensitizers offering advanced targeted delivery, improved photodynamic dose combined with modern light delivery technologies. This review surveys the available PDT treatments and emerging novel developments in the field with a particular focus on two-photon techniques that are anticipated to improve the effectiveness of PDT in tissues at depth and on next generation drugs that work without the need of the presence of oxygen for photosensitization making them effective where hypoxia has taken hold.

Influence of charge transfer on the isomerisation of stilbene derivatives for application in cancer therapy

“…Combretastatins are functionalised stilbene derivatives and therefore exist in two isomeric forms, cis and trans. It is cis-CA4 that is cytotoxic, and this species can be generated by photoisomerisation of the trans-CA4 [ 7 ], which is considerably less toxic [ [8][9][10][11]. We previously reported that the usual one-photon excitation wavelength of the latter is around 340 nm [ 12 ], which is too short for physiological use, because tissue absorption below 400 nm is high.…”

Hydrogels: soft matters in photomedicine

“…New strategies range from dyes with improved photophysical properties (long-wavelength absorbing pigments with high absorption coefficients and larger triplet quantum yields), 27 synthesis of bioconjugates with suitable targeting groups (e.g., peptides, carbohydrates, antibodies), 32,33 multimodality compounds with covalently attached effector groups (e.g., chemotherapeutics, anti-inflammatory residues), 34,35 complex superstructured singlet oxygen generating systems, 36 to the use of concepts such as photon-up-conversion for the design of suitable photoactive agents. 9,37,38 These organic synthetic strategies can be complemented by a multitude of drug delivery and formulation methods; for example, liposomes, dendrimers, nanoparticles, and nanocarriers. 39,40,41,42 In fact, the distinction between classic single molecule drugs, multimodality systems, 43 formulations, co-delivery systems, combination therapies, 44 and complex photoactive materials in the field of PDT becomes more and more blurry.…”

“…Protoporphyrin IX (38), as a natural compound, is a good PS candidate regarding its biocompatibility. Nevertheless, it has low solubility in aqueous media and tends to form aggregates.…”

Anticancer Photodynamic Therapy Using Ruthenium(II) and Os(II)-Based Complexes as Photosensitizers

“…The most commonly considered are the two types dependent on oxygen and associated with ROS production: electron transfer from the excited PS generating hydroxyl radical OH among other species (Type I) and energy transfer to a ground-state molecular oxygen 3O2 generating singlet oxygen 1O2 and superoxide radical anions (Type II) [2]. It is proposed that two more types are possible and are oxygen-independent: Type III as the interaction of the activated PS with native free radicals and Type IV as light-induced structural changes in PS allowing it to bind to subcellular targets [3].…”