Photodynamic therapy: apoptosis, paraptosis and beyond
- PDF / 576,344 Bytes
- 5 Pages / 595.276 x 790.866 pts Page_size
- 76 Downloads / 214 Views
REVIEW
Photodynamic therapy: apoptosis, paraptosis and beyond David Kessel1 Accepted: 30 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Photodynamic therapy (PDT) is a light-catalyzed process that can initiate cellular death pathways from the formation of cytotoxic reactive oxygen species at sub-cellular sites. Apoptosis was the first such pathway to be identified. Autophagy can also occur and is often found to be cytoprotective. Another process termed paraptosis can also have lethal consequences, even in cells with an impaired apoptotic pathway. PDT in vivo can evoke other potentially cytotoxic processes including vascular shutdown and enhanced immunologic recognition of neoplastic cells. Using appropriate photosensitizing agents, sub-cellular PDT targeting can be directed so that the resulting interplay among assorted death and survival pathways will result in an enhanced level of photokilling. Keywords Apoptosis · Autophagy · Paraptosis · Photodynamic
Introduction The potential for using drugs + light to eradicate certain microorganisms was reported 120 years ago [1]. This process, described as ‘photodynamic therapy’, was later found to have anti-tumor implications. Photosensitizing agents can become preferentially localized in neoplastic tissues. Upon irradiation with UV light, the resulting fluorescence can be used to visualize malignant lesions [2, 3]. Moreover, irradiation at high photon fluxes in the visible light range can lead to death of photosensitized cell types [4, 5]. Several reviews on the topic have appeared [6–11]. The PDT literature initially consisted mainly of pre-clinical reports and clinical case studies along with news on device development. This changed in 1991 when apoptosis was identified as a PDTassociated death pathway [12]. An initial study [13] and a more detailed report [14] revealed that phototoxic effects derived from the light-catalyzed formation of reactive oxygen species (ROS) in close proximity to subcellular sites of photosensitizer binding. In addition to apoptosis, PDT can elicit an autophagic response that is often cytoprotective [15]. More recently, a process termed paraptosis has been identified as a response to ER photodamage [16]. This * David Kessel [email protected] 1
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, USA
is characterized by a series of vacuoles that eventually fill the cytoplasmic space [17]. In this summary, aspects of the interplay between apoptosis, paraptosis and autophagy will be discussed along with the ability of appropriate targeting of sub-cellular loci to promote PDT efficacy.
Death pathways The first report on a death pathway associated with PDT was provided by Oleinick’s group at Case-Western Reserve University in 1991 [12]. Irradiation of photosensitized cells resulted in the rapid initiation of apoptosis, a process involving the cleavage of DNA, and subsequently cells, into fragments. A few years later, Wang et al. described a route to apoptosis
Data Loading...
