Emerging extracellular vesicle-based carriers for glioblastoma diagnosis and therapy

Wang, Jingjing; Liu, Yue; Liu, Fengbo; Gan, Shaoyan; Roy, Shubham; Hasan, Ikram; Zhang, Baozhu; Guo, Bing

doi:10.1039/d3nr01667f

Cited by 13 publications

(12 citation statements)

References 172 publications

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“…The BBB has a complex structure formed by multiple layers, including brain microvascular nonfenestrated endothelial cells sealed by junctional complexes, and is surrounded by the end feet of glial cells on the outer face. The physiological barrier is the result of a series of physical, transport, and metabolic processes within endothelial cells that are highly coordinated by interactions with different vascular, immune, and neural cell types [38][39][40]. Therefore, the BBB is not only a physical barrier, but it also actively uses endothelial efflux transporters to pump small lipophilic molecules that can diffuse through the plasma membrane back in the bloodstream.…”

Section: Blood-brain Barriermentioning

confidence: 99%

Challenges and Promise for Glioblastoma Treatment through Extracellular Vesicle Inquiry

Liguori

2024

Cells

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Glioblastoma (GB) is a rare but extremely aggressive brain tumor that significantly impacts patient outcomes, affecting both duration and quality of life. The protocol established by Stupp and colleagues in 2005, based on radiotherapy and chemotherapy with Temozolomide, following maximum safe surgical resection remains the gold standard for GB treatment; however, it is evident nowadays that the extreme intratumoral and intertumoral heterogeneity, as well as the invasiveness and tendency to recur, of GB are not compatible with a routine and unfortunately ineffective treatment. This review article summarizes the main challenges in the search for new valuable therapies for GB and focuses on the impact that extracellular vesicle (EV) research and exploitation may have in the field. EVs are natural particles delimited by a lipidic bilayer and filled with functional cellular content that are released and uptaken by cells as key means of cell communication. Furthermore, EVs are stable in body fluids and well tolerated by the immune system, and are able to cross physiological, interspecies, and interkingdom barriers and to target specific cells, releasing inherent or externally loaded functionally active molecules. Therefore, EVs have the potential to be ideal allies in the fight against GB and to improve the prognosis for GB patients. The present work describes the main preclinical results obtained so far on the use of EVs for GB treatment, focusing on both the EV sources and molecular cargo used in the various functional studies, primarily in vivo. Finally, a SWOT analysis is performed, highlighting the main advantages and pitfalls of developing EV-based GB therapeutic strategies. The analysis also suggests the main directions to explore to realize the possibility of exploiting EVs for the treatment of GB.

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Section: Blood-brain Barriermentioning

confidence: 99%

Challenges and Promise for Glioblastoma Treatment through Extracellular Vesicle Inquiry

Liguori

2024

Cells

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“…Over the last few decades, the role of extracellular vesicles (EVs) in cancer development and progression have been extensively investigated [ 10 , 11 , 12 ]. Efforts have been made to elucidate the EV cargo in relation to the source and to assess the practical and clinical value of EVs for diagnosis and patient monitoring.…”

Section: Introductionmentioning

confidence: 99%

Hsp70 and Calcitonin Receptor Protein in Extracellular Vesicles from Glioblastoma Multiforme: Biomarkers with Putative Roles in Carcinogenesis and Potential for Differentiating Tumor Types

Alberti,

Sánchez-López,

Marcilla

et al. 2024

IJMS

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Glioblastoma multiforme (GBM) is a malignancy of bad prognosis, and advances in early detection and treatment are needed. GBM is heterogenous, with varieties differing in malignancy within a tumor of a patient and between patients. Means are needed to distinguish these GMB forms, so that specific strategies can be deployed for patient management. We study the participation of the chaperone system (CS) in carcinogenesis. The CS is dynamic, with its members moving around the body in extracellular vesicles (EVs) and interacting with components of other physiological systems in health and disease, including GBM. Here, we describe the finding of high amounts of Hsp70 (HSPA1A) and the calcitonin receptor protein (CTR) in EVs in patients with GBM. We present a standardized protocol for collecting, purifying, and characterizing EVs carrying Hsp70 and CTR in plasma-derived EVs from patients with GBM. EVs from GBM patients were obtained just before tumor ablative surgery (T0) and 7 days afterwards (T1); Hsp70 was highly elevated at T0 and less so at T1, and CTR was greatly increased at T0 and reduced to below normal values at T1. Our results encourage further research to assess Hsp70 and CTR as biomarkers for differentiating tumor forms and to determine their roles in GBM carcinogenesis.

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“…Recent research has provided evidence that extracellular vehicles (EVs) possess advantageous characteristics such as excellent biocompatibility, a high capacity for carrying drugs, extended circulation duration, efficient crossing of the blood-brain barrier (BBB), targeted delivery to affected areas, and effective transport of diverse cargos for the treatment of GBM [15]. Significantly, EVs possess physiological and pathological components derived from the originating cells, making them valuable biomarkers for molecularly monitoring the malignant advancement of GBMs [16]. Moreover, the utilization of nanocarriers presents the potential to enhance the effectiveness and safety of diverse therapeutic interventions through the synergistic combination of these treatments [17].…”

Section: Introductionmentioning

confidence: 99%

Advances in Glioblastoma Therapy: An Update on Current Approaches

Angom,

Nakka,

Bhattacharya

2023

Brain Sciences

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Glioblastoma multiforme (GBM) is a primary malignant brain tumor characterized by a high grade of malignancy and an extremely unfavorable prognosis. The current efficacy of established treatments for GBM is insufficient, necessitating the prompt development of novel therapeutic approaches. The progress made in the fundamental scientific understanding of GBM is swiftly translated into more advanced stages of therapeutic studies. Despite extensive efforts to identify new therapeutic approaches, GBM exhibits a high mortality rate. The current efficacy of treatments for GBM patients is insufficient due to factors such as tumor heterogeneity, the blood–brain barrier, glioma stem cells, drug efflux pumps, and DNA damage repair mechanisms. Considering this, pharmacological cocktail therapy has demonstrated a growing efficacy in addressing these challenges. Towards this, various forms of immunotherapy, including the immune checkpoint blockade, chimeric antigen receptor T (CAR T) cell therapy, oncolytic virotherapy, and vaccine therapy have emerged as potential strategies for enhancing the prognosis of GBM. Current investigations are focused on exploring combination therapies to mitigate undesirable side effects and enhance immune responses against tumors. Furthermore, clinical trials are underway to evaluate the efficacy of several strategies to circumvent the blood–brain barrier (BBB) to achieve targeted delivery in patients suffering from recurrent GBM. In this review, we have described the biological and molecular targets for GBM therapy, pharmacologic therapy status, prominent resistance mechanisms, and new treatment approaches. We also discuss these promising therapeutic approaches to assess prospective innovative therapeutic agents and evaluated the present state of preclinical and clinical studies in GBM treatment. Overall, this review attempts to provide comprehensive information on the current status of GBM therapy.

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Emerging extracellular vesicle-based carriers for glioblastoma diagnosis and therapy

Abstract: Glioblastoma (GBM) is still a big clinic challenge because of its highly malignant, invasive, and lethal characteristics. After the treatment with conventional therapeutic paradigm of surgery combined with radiotherapy and...

Cited by 13 publications

References 172 publications

Challenges and Promise for Glioblastoma Treatment through Extracellular Vesicle Inquiry

Challenges and Promise for Glioblastoma Treatment through Extracellular Vesicle Inquiry

Hsp70 and Calcitonin Receptor Protein in Extracellular Vesicles from Glioblastoma Multiforme: Biomarkers with Putative Roles in Carcinogenesis and Potential for Differentiating Tumor Types

Advances in Glioblastoma Therapy: An Update on Current Approaches

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