Advance in Photosensitizers and Light Delivery for Photodynamic Therapy

Abstract

The brief history of photodynamic therapy (PDT) research has been focused on photosensitizers (PSs) and light delivery was introduced recently. The appropriate PSs were developed from the first generation PS Photofrin (QLT) to the second (chlorins or bacteriochlorins derivatives) and third (conjugated PSs on carrier) generations PSs to overcome undesired disadvantages, and to increase selective tumor accumulation and excellent targeting. For the synthesis of new chlorin PSs chlorophyll a is isolated from natural plants or algae, and converted to methyl pheophorbide a (MPa) as an important starting material for further synthesis. MPa has various active functional groups easily modified for the preparation of different kinds of PSs, such as methyl pyropheophorbide a, purpurin-18, purpurinimide, and chlorin e6 derivatives. Combination therapy, such as chemotherapy and photothermal therapy with PDT, is shortly described here. Advanced light delivery system is shown to establish successful clinical applications of PDT. Phtodynamic efficiency of the PSs with light delivery was investigated in vitro and/or in vivo.

Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer, antimicrobial and immunosuppressive agents

“…It also has to be prepared by a reliable and cost-effective synthesis and has to be a stable, pure compound that is not toxic in the absence of light, but is efficient in generating singlet oxygen or other ROS upon red light activation. The generally accepted requirements that one has to take into account at the beginning of a search for a new PS also include easy administration and distribution (Vicente 2001;Pushpan et al 2002;Ethirajan et al 2011;Yoon et al 2013;Mehraban and Freeman 2015). Porphyrin-type compounds (Fig.…”

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

“…chlorins, bacteriochlorins and phthalocyanines) were developed. Third generation PSs were designed to improve selective tumour targeting and drug accumulation by conjugating common PSs to carriers such as cholesterol, antibodies, and liposomes and therefore reduce unwanted damage to healthy tissues [5,42,69,78]. The section on targeted PDT below (4.7) will cover these developments in more detail.…”

“…First generation PSs such as Photofrin® and HpD were found to lead to extended skin photosensitivity and are often given as part of a palliative care pathway [5,42]. To overcome the undesired photosensitization caused by first generation PSs and shift the PS activation to longer wavelengths second generation PSs (e.g.…”

“…Type III PSs are usually Antioxidant Carrier Sensitizers (ACS), also called Modified Type I (MTO) PSs, which combine properties leading to the efficient generation of singlet oxygen and decreasing the concentration of native free radicals in malignant cells. ACS are usually synthesized from the molecular backbone of originally active PSs used in clinical PDT, such as substituted porphyrin derivatives [5,10,15,17,19,24,26,28,29,[40][41][42][43][44]. Currently novel types of pro-drugs such as combretastatins, discussed fully in section 4.4, are emerging which can be directly photo- activated by multiphoton excitation without the need for the presence of oxygen within the target tissue (see the section on Alternative Strategy for Two-photon Phototherapy (2P-PDT) without ROS below).…”

Photodynamic therapy of tumors with pyropheophorbide-<em>a</em>-loaded polyethylene glycol&ndash;poly(lactic-<em>co</em>-glycolic acid) nanoparticles

“…The targeted delivery of Pyro will reduce the effective dose administered and skin photosensitivity by increasing the accumulation of PSs inside tumor tissues. 23,24 Maximizing tumor-tissue selectivity and reducing normal tissue or skin accumulation is very important for improving the therapeutic outcome of Pyro in PDT.…”