Nanomedicine associated with photodynamic therapy for glioblastoma treatment

Abstract

Glioblastoma, also known as glioblastoma multiforme (GBM), is the most recurrent and malignant astrocytic glioma found in adults. Biologically, GBMs are highly aggressive tumors that often show diffuse infiltration of the brain parenchyma, making complete surgical resection difficult. GBM is not curable with surgery alone because tumor cells typically invade the surrounding brain, rendering complete resection unsafe. Consequently, present-day therapy for malignant glioma remains a great challenge. The location of the invasive tumor cells presents several barriers to therapeutic delivery. The blood-brain barrier regulates the trafficking of molecules to and from the brain. While high-grade brain tumors contain some "leakiness" in their neovasculature, the mechanisms of GBM onset and progression remain largely unknown. Recent advances in the understanding of the signaling pathways that underlie GBM pathogenesis have led to the development of new therapeutic approaches targeting multiple oncogenic signaling aberrations associated with the GBM. Among these, drug delivery nanosystems have been produced to target therapeutic agents and improve their biodistribution and therapeutic index in the tumor. These systems mainly include polymer or lipid-based carriers such as liposomes, metal nanoparticles, polymeric nanospheres and nanocapsules, micelles, dendrimers, nanocrystals, and nanogold. Photodynamic therapy (PDT) is a promising treatment for a variety of oncological diseases. PDT is an efficient, simple, and versatile method that is based on a combination of a photosensitive drug and light (generally laser-diode or laser); these factors are separately relatively harmless but when used together in the presence of oxygen molecules, free radicals are produced that initiate a sequence of biological events, including phototoxicity, vascular damage, and immune responses. Photodynamic pathways activate a cascade of activities, including apoptotic and necrotic cell death in both the tumor and the neovasculature, leading to a permanent lesion and destruction of GBM cells that remain in the healthy tissue. Glioblastoma tumors differ at the molecular level. For example, gene amplification epidermal growth factor receptor and its receptor are more highly expressed in primary GBM than in secondary GBM. Despite these distinguishing features, both types of tumors (primary and secondary) arise as a result dysregulation of numerous intracellular signaling pathways and have standard features, such as increased cell proliferation, survival and resistance to apoptosis, and loss of adhesion and migration, and may show a high degree of invasiveness. PDT may promote significant tumor regression and extend the lifetime of patients who experience glioma progression.

Dual Role of Subphthalocyanine Dyes for Optical Imaging and Therapy of Cancer

“…The results obtained, shown in Table 2 , indicate that none of these SubPc concentrations, neither the administration of green light, induced significant cytotoxic effects in the cell lines studied, and survival rates above 92% were obtained. We then continued to evaluate the photodynamic activity of the three SubPcs toward SCC‐13, HeLa, and A431 cells upon irradiation . For the photodynamic treatments, we selected the lower noncytotoxic SubPc concentration (i.e., 5 × 10 −8 m ) and, after 5 h of incubation, cells were exposed to different green light doses (2, 3.35, and 4.7 J cm −2 ).…”

Photodynamic Therapy for the Treatment of Glioblastoma

“…First-generation photosensitizer molecules consist of naturally occurring porphyrins, including hematoporphyrin ( Table 1). These compounds have a strong absorption around 400 nm but have limited excitation absorption at longer wavelengths of light (22). HpD is an example of a first generation photosensitizer.…”

Effect of Photosensitizers Photosens, Photodithazine and Hypericin on Glioma Сells and Primary Neuronal Cultures: a Comparative Analysis

“…Despite the fact that tumor growth is accompanied by BBB damage and an increase in its permeability, the use of drugs and their entry into tumor is impeded [7]. Screening of currently known cytostatic agents has revealed their low efficiency in brain tumor therapy, resulting in a limited list of officially approved drugs for malignant gliomas treatment [8,9]. Thus, prognoses for patients with malignant glioma are still extremely unfavorable, even in case of using advanced treatment techniques.…”

“…Photodynamic therapy (PDT) is regarded as the most attractive strategy for effective adjuvant therapy of gliomas [11]. The method suggests the use of photosensitizers able to cross BBB and selectively accumulate in tumor [9,12]. When exposed to visible light irradiation, an activated photosensitizer generates singlet oxygen and radical active oxygen species that have a direct cytotoxic effect on tumor cells causing their death, including an immunogenic pathway [13].…”