Application of photodynamic therapy drugs for management of glioma

Abstract

Human gliomas are one of the most prevalent and challenging-to-treat adult brain tumors, and thus result in high morbidity and mortality rates worldwide. Current research and treatments of gliomas include surgery associated with conventional chemotherapy, use of biologicals, radiotherapy, and medical device applications. The selected treatment options are often guided by the category and aggressiveness of this deadly disease and the patient’s conditions. However, the effectiveness of these approaches is still limited due to poor drug efficacy (including delivery to desired sites), undesirable side effects, and high costs associated with therapies. In addition, the degree of leakiness of the blood–brain barrier (BBB) that regulates trafficking of molecules in and out of the brain also modulates accumulation of adequate drug levels to tumor sites. Active research is being pursued to overcome these limitations to obtain a superior therapeutic index and enhanced patient survival. One area of development in this direction focuses on the localized application of photodynamic therapy (PDT) drugs to cure brain cancers. PDT molecules potentially utilize multiple pathways based on their ability to generate reactive oxygen species (ROS) upon photoactivation by a suitable light source. In this communication, we have attempted to provide a brief overview of PDT and cancer, photoactivation pathways, mechanism of tumor destruction, effect of PDT on tumor cell viability, immune activation, various research attempted by applying PDT in combination with novel strategies to treat glioma, role of BBB and clinical status of PDT therapy for glioma treatment.

Photodynamic therapy and associated targeting methods for treatment of brain cancer

“…In PDT irreversible destruction of neoplastic tissue can occur in several ways ( de Paula et al, 2017 ). The first is direct cell death via apoptosis, necrotic cell death or autophagy, with apoptosis being the predominantly preferred mechanism ( DUBEY et al, 2019 ). Apoptosis is characterized by nuclear fragmentation, chromatin condensation and formation of apoptotic bodies, while necrotic cell death is characterized by destruction of organelles, disruption of the plasma membrane and induction of an immune response ( DUBEY et al, 2019 ).…”

Novel Iron-Chelating Prodrug Significantly Enhanced Fluorescence-Mediated Detection of Glioma Cells Experimentally In Vitro

“…Glioma consists of a complex mass of different cell types, and whilst the cell model employed in this study was an effective tool for initial experimentation with the novel iron-chelating PpIX-prodrug AP2-18, as with every model, it was highly simplified in comparison to the complex system that it represented [ 39 , 40 ]. For example, the way the drugs interact with the blood–brain barrier, and its permeability may have an impact on PpIX accumulation in practice [ 41 ]. PDT effectiveness may also depend upon the cellular environment in which it is acting.…”

Photodynamic therapy of malignant brain gliomas

“…Фотодинамічна терапія була впровад жена як варіант місцевого (локального) хірургічного лікування, що ґрунтується на цитотоксичних ефектах, спричинених хімічним фотосенсибілізувальним агентом, який селективно накопичується в злоякісній тканині пухлини і активується світловими променями відповідної довжини хвилі [32,33], генеруючи синглетний кисень та вільні радикали, які запускають у пухлинних клітинах фотохімічні реакції з подальшим руйнуванням їхніх білкових структур. Фотодинамічна терапія передбачає фотоактивацію молекули ФС, що селективно включається в неопластичні клітини [34].…”