H2S Photosystems in the Treatment of Glioblastoma

Abstract

Glioblastoma multiforme (GBM) is the most frequent and deadly primary malignant central nervous system (CNS) tumour in adults. GBM is usually treated through the reduction of tumour mass and cerebral decompression, together with radiotherapy and chemotherapy, which improve the quality of life of the subject and prolong its survival. Treatment remains challenging, as GBM inevitably re‐emerges despite surgical debulking, radiotherapy and chemotherapy. Therefore, the discovery of effective therapy for GBM is an area of interest. Photothermal therapy (PTT) is a newly developed and encouraging therapeutic strategy, in treating cancer. Gold nanorods (AuNRs) are ideal nanomaterials for PTT applications both in vitro and in vivo. There is a reasonable body of evidence suggesting that endogenous H2S production is important for the growth and proliferation of colon and ovarian cancer. A limited number of studies are available in CNS cancer. Photoresponsive systems that delivers H2S on demand were used to treat glioblastoma to design and generate compounds based on photo‐thermal release of H2S that act as anti‐cancer therapy for glioblastoma. AuNRDs were prepared by a modified procedure based on the seed assisted method. These systems were tailored with a thiolate spacer appendages to permit the covalently link to the AuNRDs surface. The dual H2S photoactive‐systems were characterized by electronic microscopy methods, optical absorption, and emission techniques. Photocontrolled H2S‐based therapies were tested on GBM cell lines U87, A172, U138, LN‐18, T98G, U118‐MG. Measurement of H2S relase, Cell Cycle Analysis, Comet assay, determination of intracellular ROS, and apoptotic pathways were performed. Moreover, xenograft and orthotopic model were used to demonstrated the effect of dual H2S photoactive‐systems on tumour volume and weight, neoangiogenesis, tissue invasion. Animals were also subjected to magnetic resonance imaging. Photocontrolled H2S‐based therapies could emerge as new unconventional treatment modalities that complement better‐known photodynamic and photothermal therapies. Nanosystems carrying chemotherapeutic drugs or as mediators of alternative therapies offer several advantages over the standard dosing forms in the treatment of GBM.Support or Funding Informationno funding