Current Photodynamic Therapy for Glioma Treatment: An Update Photodynamic Therapy in the Treatment of Brain Gliomas
Photodynamic therapy is applied for the treatment of neurological diseases and many types of brain tumors [
123]. Photodynamic therapy has fewer side effects compared to chemotherapy and radiotherapy on the brain. After administration, the concentration of PSs is higher in glioma cells than in healthy tissue [
31,
124]. When combined with surgical resection, PDT for the treatment of gliomas, or alternatively as a stand-alone treatment strategy, has had some success in extending median patient survival compared to surgery alone [
125]. The immunological effects of PDT are of particular interest given recent studies demonstrating the importance of these processes in glioma [
126,
127]. However, the use of this method in the treatment of gliomas also has some limitations. The main drawback is the development of resistance to PDT in tumors. Several mechanisms are known to be involved in the development of cellular defense against the cytotoxic effects of PDT, including activation of antioxidant enzymes, drug efflux pumps, PS degradation, and overexpression of chaperones [
128].
DNA repair may aid in glioma resistance to PDT; however, this has not been further explored to date [
129]. Many biological barriers may have an influence on the results of glioma PDT [
9]. These include technical limitations of light delivery [
130]. However, the problem of delivering light to the tumor, at least in some cases, can be solved by using implantable devices that enable light delivery during PDT, or near-infrared lasers that allow tissue penetration of up to 3 cm [
9]. The effectiveness of glioma-PDT is based on the activation of PSs accumulated in the tumor with light. However, insufficient accumulation of PSs in the tumor severely limits the success of PDT [
131]. The blood–brain barrier (BBB) is a significant limitation of PS transport to the area of postoperative resection, where brain tumor recurrence most often occurs [
132,
133]. In order to develop the “ideal photosensitizer”,
there is still a need for new photodynamic agents with improved photophysical and photobiological properties [
134]. Recent research has also led to the discovery of profound genetic heterogeneity among glioma cells that includes the adaptation to ROS. Therefore, tumor heterogeneity and the associated difference in sensitivity to ROS-producing therapeutic agents must be taken into account when designing PDT protocols to predict outcomes [
135]. Moreover, there are no standard guidelines for PDT treatment protocols, and it is known that the selection of parameters affects the quality of treatment. Further observations are needed to further assess how PDT will reduce morbidity and mortality [
136,
137,
138].
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