Treatment Of Glioblastoma Multiforme Research Articles

Hybrid Membrane Biomimetic Photothermal Nanorobots for Enhanced Chemodynamic-Chemotherapy-Immunotherapy.

Glioblastoma multiforme (GBM) is a highly invasive and fatal brain tumor with a grim prognosis, where current treatment modalities, including postoperative radiotherapy and temozolomide chemotherapy, yield a median survival of only 15 months. The challenges of tumor heterogeneity, drug resistance, and the blood-brain barrier necessitate innovative therapeutic approaches. This study introduces a strategy employing biomimetic magnetic nanorobots encapsulated with hybrid membranes derived from platelets and M1 macrophages to enhance blood-brain barrier penetration and target GBM. The nanorobots encapsulate a polypyrrole/Fe3O4 nanocomplex (PPy@F) for photothermal therapy (PTT) and promote the Fenton reaction of Fe3O4 to generate chemodynamic therapy (CDT). Additionally, temozolomide and PD-L1 antibody (SNTSESF) act as chemotherapy drug and immune checkpoint inhibitor, respectively. The biomimetic design leverages the functional properties of cell membranes to improve the blood residence time and tumor targeting. The integration of PTT and CDT aims to transform "cold" tumors into "hot" tumors, thereby enhancing immunotherapeutic efficacy. This multifaceted approach, PTT, CT, CDT, and immune checkpoint blockade therapy, offers a promising strategy for the treatment of GBM.

Expression of some circulating microRNAs as predictive biomarkers for prognosis and treatment response in glioblastoma

Glioblastoma multiforme (GBM) is the most prevalent, treatment-resistant, and fatal form of brain malignancy. It is characterized by genetic heterogeneity, and an infiltrative nature, and GBM treatment is highly challenging. Despite multimodal therapies, clinicians lack efficient prognostic and predictive markers. Therefore, new insights into GBM management are urgently needed to increase the chance of therapeutic success. Circulating miRNAs (miRs) are important regulators of cancer progression and are potentially useful for GBM diagnosis and treatment. This study investigated how miR-29a, miR-106a, and miR-200a affect the prognosis of GBM patients. This study was conducted on 25 GBM patients and 20 healthy volunteers as a control group. The expression levels of target miRs were analyzed pre- and post-treatment using qRT-PCR and evaluated in relation to both clinical GBM criteria and the patient’s survival modes. The diagnostic efficacy of target miRs was assessed using the receiver operating characteristic (ROC) curve. MiRs levels showed significant differences among the enrolled participants. All investigated miRs were significantly elevated in GBM patients with non-frontal lesions. Only miR-200a showed a significant difference in GBM patients older than 60 years with a tumor size ≥ 5 mm. Regarding miR-106a, a significant difference was detected based on the surgical strategy and use of an Eastern Cooperative Oncology Group (ECOG) performance status equal to 2. For miR-29a, a significant upregulation was detected according to the surgical strategy. All post-treatment miRs levels in GBM patients were significantly downregulated. In conclusion, circulating miRs revealed a significant role in predicting GBM patient treatment outcomes providing valuable insights for personalized therapeutic strategies.

Poly Lactic Co-glycolic Acid d-α-tocopheryl Polyethylene Glycol 1000 Succinate Fabricated Polyethylene Glycol Hybrid Nanoparticles of Imatinib Mesylate for the Treatment of Glioblastoma Multiforme.

This study aimed to develop Imatinib Mesylate (IMT)-loaded Poly Lactic-co-Glycolic Acid (PLGA)-D-α-tocopheryl polyethylene glycol succinate (TPGS)- Polyethylene glycol (PEG) hybrid nanoparticles (CSLHNPs) with optimized physicochemical properties for targeted delivery to glioblastoma multiforme. Glioblastoma multiforme (GBM) is the most destructive type of brain tumor with several complications. Currently, most treatments for drug delivery for this disease face challenges due to the poor blood-brain barrier (BBB) and lack of site-specific delivery. Imatinib Mesylate (IMT) is one of the most effective drugs for GBM, but its primary issue is low bioavailability. Therefore, nanotechnology presents a promising solution for targeted IMT delivery to GBM. This article primarily explores the fabrication of IMT-loaded core-shell lipid-polymer hybrid nanoparticles (CSLHNPs) to achieve enhanced brain delivery with therapeutic efficacy. The primary objective of this study is to develop optimized, stable IMT-loaded hybrid nanoparticles with an encapsulated polymer matrix and to evaluate these nanoparticles using sophisticated instruments such as SEM and TEM to achieve smooth, spherical nanoparticles in a monodispersed phase. The enhanced stable formulation yielded a notable increase in entrapment efficiency, reaching 58.89 ± 0.5%. The physical stability analysis of nanoparticles was assessed over 30 days under conditions of 25 ± 2°C and 60 ± 5% relative humidity. Hemolytic assays affirmed the biocompatibility and safety profile of the nanoparticles. in vitro drug release kinetics revealed a sustained IMT release over 48 hours. The formulated CSLHNPs achieved a narrow size distribution with a mean vesicle diameter of 155.03 ± 2.41 nm and a low polydispersity index (PDI) of 0.23 ± 0.4, indicating monodispersity. A high negative zeta potential of -23.89 ± 3.47 mV ensured excellent colloidal stability in physiological conditions. XRD analysis confirmed the successful encapsulation of IMT within the nanoparticle matrix, with the drug transitioning to an amorphous state for enhanced dissolution. During Cell-Cell viability assays on LN229, glioblastoma cells were treated with IMT-loaded nanoparticles and showed a significantly enhanced inhibitory effect compared to free IMT. These hybrid nanoparticles demonstrated potential in reducing oxidative stress-induced cellular damage by mitigating reactive oxygen species (ROS). Thus, the prepared IMT hybrid nanoparticles showed higher cellular uptake and superior cytotoxicity compared to the plain drug. This study posits the IMT-PLGA-TPGS-DSPE PEG 2000-CSPLHNPs as a formidable and innovative drug delivery system for Glioblastoma Multiforme (GBM) treatment, warranting further exploration into their clinical application potential. Future work could involve conducting in vivo studies to evaluate the pharmacokinetics, biodistribution, and therapeutic efficacy of the IMT-PLGA-TPGS-DSPE PEG 2000-CSPLHNPs in animal models of Glioblastoma Multiforme (GBM). Additionally, further research may focus on optimizing the nanoparticle formulation for enhanced targeting capabilities, investigating long-term stability under varied storage conditions, exploring potential combination therapies to synergize with the nanoparticles, and assessing the scalability and manufacturability of the developed drug delivery system for potential clinical translation. Integration of advanced imaging techniques for real- time tracking and visualization of nanoparticle distribution within tumours could also be a promising direction for future investigations.

A Theoretical Study on the Efficacy and Mechanism of Combined YAP-1 and PARP-1 Inhibitors in the Treatment of Glioblastoma Multiforme Using Peruvian Maca Lepidium meyenii

Glioblastoma multiforme (GBM) is one of the most aggressive and treatment-resistant forms of brain cancer. Current therapeutic strategies, including surgery, chemotherapy, and radiotherapy, often fail due to the tumor’s ability to develop resistance. The proteins YAP-1 (Yes-associated protein 1) and PARP-1 (Poly-(ADP-ribose)–polymerase-1) have been implicated in this resistance, playing crucial roles in cell proliferation and DNA repair mechanisms, respectively. This study explored the inhibitory potential of natural compounds from Lepidium meyenii (Peruvian Maca) on the YAP-1 and PARP-1 protein systems to develop novel therapeutic strategies for GBM. By molecular dynamics simulations, we identified N-(3-Methoxybenzyl)-(9Z,12Z,15Z)- octadecatrienamide (DK5) as the most promising natural inhibitor for PARP-1 and stearic acid (GK4) for YAP-1. Although synthetic inhibitors, such as Olaparib (ODK) for PARP-1 and Verteporfin (VER) for YAP-1, only VER was superior to the naturally occurring molecule and proved a promising alternative. In conclusion, natural compounds from Lepidium meyenii (Peruvian Maca) offer a potentially innovative approach to improve GBM treatment, complementing existing therapies with their inhibitory action on PARP-1 and YAP-1.

A fetal oncogene NUAK2 is an emerging therapeutic target in glioblastoma.

Glioblastoma Multiforme (GBM) is the most prevalent and highly malignant form of adult brain cancer characterized by poor overall survival rates. Effective therapeutic modalities remain limited, necessitating the search for novel treatments. Neurodevelopmental pathways have been implicated in glioma formation, with key neurodevelopmental regulators being re- expressed or co-opted during glioma tumorigenesis. Here we identified a serine/threonine kinase, NUAK family kinase 2 (NUAK2), as a fetal oncogene in mouse and human brains. We found robust expression of NUAK2 in the embryonic brain that decreases throughout postnatal stages and then is re-expressed in malignant gliomas. However, the role of NUAK2 in GBM tumorigenesis remains unclear. We demonstrate that CRIPSR-Cas9 mediated NUAK2 deletion in GBM cells results in suppression of proliferation, while overexpression leads to enhanced cell growth in both in vitro and in vivo models. Further investigation of the downstream biological processes dysregulated in the absence of NUAK2 reveals that NUAK2 modulates extracellular matrix (ECM) components to facilitate migratory behavior. Lastly, we determined that pharmaceutical inhibition of NUAK2 is sufficient to impede the proliferation and migration of malignant glioma cells. Our results suggest that NUAK2 is an actionable therapeutic target for GBM treatment.

Immunotherapy against glioblastoma using backpack-activated neutrophils.

Immune checkpoint inhibitors (ICIs) represent new therapeutic candidates against glioblastoma multiforme (GBM); however, their efficacy is clinically limited due to both local and systemic immunosuppressive environments. Hence, therapeutic approaches that stimulate local and systemic immune environments can improve the efficacy of ICIs. Here, we report an adoptive cell therapy employing neutrophils (NE) that are activated via surface attachment of drug-free disk-shaped backpacks, termed Cyto-Adhesive Micro-Patches (CAMPs) for treating GBM. CAMP-adhered neutrophils (NE/CAMPs) significantly improved the efficacy of an anti-PD1 antibody (aPD-1) in a subcutaneous murine GBM model (GL261). A combination of NE/CAMPs and aPD-1 completely regressed subcutaneous GL261 tumors in mice. The efficacy of NE/CAMPs against GBM was also tested in an orthotopic GL261 model. Neutrophil's ability to migrate into the brain was not affected by CAMP attachment, and intracerebral NE/CAMP accumulation was observed in mice-bearing orthotopic GBM. The combination treatment of NE/CAMPs and aPD-1 activated systemic immune responses mediated by T cells and showed improved therapeutic responses compared with aPD-1 alone in the orthotopic GBM model. These results suggest that immunomodulation with NE/CAMPs offers a potential approach for the treatment of GBM by combination with ICIs.

Monitoring of cancer ferroptosis with [18F]hGTS13, a system xc- specific radiotracer.

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults, characterized by resistance to conventional therapies and poor survival. Ferroptosis, a form of regulated cell death driven by lipid peroxidation, has recently emerged as a promising therapeutic target for GBM treatment. However, there are currently no non-invasive imaging techniques to monitor the engagement of pro-ferroptotic compounds with their respective targets, or to monitor the efficacy of ferroptosis-based therapies. System xc-, an important player in cellular redox homeostasis, plays a critical role in ferroptosis by mediating the exchange of cystine for glutamate, thus regulating the availability of cysteine, a crucial precursor for glutathione synthesis, and influencing the cellular antioxidant defense system. We have recently reported the development and validation of [18F]hGTS13, a radiopharmaceutical specific for system xc-. Methods: In the current work, we characterized the sensitivity of various cell lines to pro-ferroptotic compounds and evaluated the ability of [18F]hGTS13 to distinguish between sensitive and resistant cell lines and monitor changes in response to ferroptosis-inducing investigational compounds. We then associated changes in [18F]hGTS13 uptake with cellular glutathione content. Furthermore, we evaluated [18F]hGTS13 uptake in a rat model of glioma, both before and after treatment with imidazole ketone erastin (IKE), a pro-ferroptotic inhibitor of system xc- activity. Results: Treatment with erastin2, a system xc- inhibitor, significantly decreased [18F]hGTS13 uptake and cellular glutathione content in vitro. Dynamic PET/CT imaging of C6 glioma-bearing rats with [18F]hGTS13 revealed high and sustained uptake within the intracranial glioma and this uptake was decreased upon pre-treatment with IKE. Conclusion: In summary, [18F]hGTS13 represents a promising tool to distinguish cell types that demonstrate sensitivity or resistance to ferroptosis-inducing therapies that target system xc-, and monitor the engagement of these drugs.

Nanocarriers in glioblastoma treatment: a neuroimmunological perspective.

Glioblastoma multiforme (GBM) is the most fatal brain tumor with a poor prognosis with current treatments, mainly because of intrinsic resistance processes. GBM is also referred to as grade 4 astrocytoma, that makes up about 15.4 % of brain cancers globally as well as 60-75 % of astrocytoma. The most prevalent therapeutic choices for GBM comprise surgery in combination with radiotherapy and chemotherapy, providing patients with an average survival of 6-14months. Nanocarriers provide various benefits such as enhanced drug solubility, biocompatibility, targeted activity, as well as minimized side effects. In addition, GBM treatment comes with several challenges such as the presence of the blood-brain barrier (BBB), blood-brain tumor barrier (BBTB), overexpressed efflux pumps, infiltration, invasion, drug resistance, as well as immune escape due to tumor microenvironment (TME) and cancer stem cells (CSC). Recent research has focused on nanocarriers due to their ability to self-assemble, improve bioavailability, provide controlled release, and penetrate the BBB. These nano-based components could potentially enhance drug accumulation in brain tumor tissues and reduce systemic toxicity, making them a compelling solution for GBM therapy. This review captures the complexities associated with multi-functional nano drug delivery systems (NDDS) in crossing the blood-brain barrier (BBB) and targeting cancer cells. In addition, it presents a succinct overview of various types of targeted multi-functional nano drug delivery system (NDDS) which has exhibited promising value for improving drug delivery to the brain.

Elimination of High-grade Gliomas Through Induced Cytolysis, Elucidated by Two Patient Cases.

Glioblastoma multiforme (GBM) is the most common and aggressive form of primary malignant tumors in the central nervous system of adults. In practice, all patients with GBM experience relapse, and treatment options become limited following first-line therapy. We previously reported a new, successful treatment approach for a GBM patient, implemented in direct conjunction with surgical intervention. Here, we present an additional case demonstrating the success of this protocol, along with an overview of its underlying rationale and mechanisms. Following maximal safe tumor resection, our protocol involves the placement of two catheters in the tumor excision bed, connected to drug infusion pumps for continuous administration. The tumor's excision beds are irrigated for 90-120 hours with a slightly alkaline Tris-buffered solution containing L-2,4 diaminobutyric acid, an unnatural amino acid, and Prazosin, a proapoptotic drug widely used as an antihypertensive. Both patients demonstrated marked clinical improvement. Recent contrast-enhanced magnetic resonance imaging revealed no evidence of malignancy, with Case 1 remaining disease-free for seven years and Case 2 for two years of follow-up. This innovative approach not only enhances local drug delivery but also minimizes systemic side effects, addressing a critical challenge in GBM treatment. These cases highlight the potential of this protocol as an adjunct to standard therapies, offering a promising option for managing inoperable or recurrent GBM.

Copper-coordination driven brain-targeting nanoassembly for efficient glioblastoma multiforme immunotherapy by cuproptosis-mediated tumor immune microenvironment reprogramming

Limited drug accumulation and an immunosuppressive microenvironment are the major bottlenecks in the treatment of glioblastoma multiforme (GBM). Herein, we report a copper-coordination driven brain-targeting nanoassembly (TCe6@Cu/TP5 NPs) for site-specific delivery of therapeutic agents and efficient immunotherapy by activating the cGAS-STING pathway and downregulating the expression of PD-L1. To achieve this, the mitochondria-targeting triphenylphosphorus (TPP) was linked to photosensitizer Chlorin e6 (Ce6) to form TPP-Ce6 (TCe6), which was then self-assembled with copper ions and thymopentin (TP5) to obtain TCe6@Cu/TP5 NPs. This nanoassembly effectively accumulated in tumor sites through the copper transport mechanism. Meanwhile, TCe6@Cu/TP5 could induce mitochondrial impairment by photodynamic therapy (PDT) mediated reactive oxygen species (ROS) accumulation and Cu2+ triggered cuproptosis, resulting in evoking the AMP-activated protein kinase (AMPK) pathway to degrade PD-L1, and activating the cGAS-STING pathway to enhance anti-tumor immunity. Moreover, TP5 significantly promoted the proliferation and differentiation of dendritic cells (DCs) and T lymphocytes to further amplify the cancer immunity cycle. Collectively, our TCe6@Cu/TP5 NPs effectively facilitate drug accumulation and activate systemic antitumor immunity in vitro and in vivo, providing an innovative solution across the BBB that potentiates GBM immunotherapy.Graphical

Injectable Tumoricidal Neural Stem Cell-Laden Hydrogel for Treatment of Glioblastoma Multiforme—An In Vivo Safety, Persistence, and Efficacy Study

Background/Objectives: Glioblastoma multiforme (GBM) is the most common high-grade primary brain cancer in adults. Despite efforts to advance treatment, GBM remains treatment resistant and inevitably progresses after first-line therapy. Induced neural stem cell (iNSC) therapy is a promising, personalized cell therapy approach that has been explored to circumvent challenges associated with the current GBM treatment. Methods: Herein, we developed a chitosan-based (CS) injectable, biodegradable, in situ forming thermo-responsive hydrogel as a cell delivery vehicle for the treatment of GBM. Tumoricidal neural stem cells were encapsulated in the injectable CS hydrogel as stem cell therapy for treatment of post-surgical GBM. In this report, we investigated the safety of the injectable CS hydrogel in an immune-competent mouse model. Furthermore, we evaluated the persistence and efficacy of iNSC-laden CS hydrogels in a post-surgical GBM mouse model. Results: The injectable CS hydrogel was well tolerated in mice with no signs of chronic local inflammation. Induced neural stem cells (iNSCs) persisted in the CS hydrogels for over 196 days in comparison to 21 days for iNSCs (cell injection) only. GBM recurrence was significantly slower in mice treated with iNSC-laden CS hydrogels with a 50% increase in overall median survival in comparison to iNSCs (cell injection) only. Conclusions: Collectively, we demonstrated the ability to encapsulate, retain, and deliver iNSCs in an injectable CS hydrogel that is well tolerated with better survival rates than iNSCs alone.

Development of a hydrogel-based three-dimensional (3D) glioblastoma cell lines culture as a model system for CD73 inhibitor response study

BackgroundDespite the development of various therapeutic approaches over the past decades, the treatment of glioblastoma multiforme (GBM) remains a major challenge. The extracellular adenosine-generating enzyme, CD73, is involved in the pathogenesis and progression of GBM, and targeting CD73 may represent a novel approach to treat this cancer. In this study, three-dimensional culture systems based on three hydrogel compositions were characterized and an optimal type was selected to simulate the GBM microenvironment. In addition, the effect of a CD73 inhibitor on GBM cell aggregates and spheroids was investigated as a potential therapeutic approach for this disease.MethodsRheology measurements, Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and cell proliferation assays were performed to analyze the synthesized hydrogel and select an optimal formulation. The viability of tumor cells in the optimal hydrogel was examined histologically and by confocal microscopy. In addition, the sensitivity of the tumor cells to the CD73 inhibitor was investigated using a cell proliferation assay and real-time PCR.ResultsThe data showed that the hydrogel containing 5 wt% gelatin and 5 wt% sodium alginate had better rheological properties and higher cell viability. Therefore, it could provide a more suitable environment for GBM cells and better mimic the natural microenvironment. GBM cells treated with CD73 inhibitors significantly decreased the proliferation rate and expression of VEGF and HIF1-α in the optimal hydrogel.ConclusionOur current research demonstrates the great potential of CD73 inhibitor for clinical translation of cancer studies by analyzing the behavior and function of 3D tumor cells, and thus for more effective treatment protocols for GBM.

Innovative Approaches to Brain Cancer: The Use of Magnetic Resonance-guided Focused Ultrasound in Glioma Therapy.

Gliomas are a wide group of common brain tumors, with the most aggressive type being glioblastoma multiforme (GBM), with a 5-year survival rate of less than 5% and a median survival time of approximately 12-14 months. The standard treatment of GBM includes surgical excision, radiotherapy, and chemotherapy with temozolomide (TMZ). However, tumor recurrence and progression are common. Therefore, more effective treatment for GBM should be found. One of the main obstacles to the treatment of GBM and other gliomas is the blood-brain barrier (BBB), which impedes the penetration of antitumor chemotherapeutic agents into glioblastoma cells. Nowadays, one of the most promising novel methods for glioma treatment is Magnetic Resonance-guided Focused Ultrasound (MRgFUS). Low-intensity FUS causes the BBB to open transiently, which allows better drug delivery to the brain tissue. Under magnetic resonance guidance, ultrasound waves can be precisely directed to the tumor area to prevent side effects in healthy tissues. Through the open BBB, we can deliver targeted chemotherapeutics, anti-tumor agents, immunotherapy, and gene therapy directly to gliomas. Other strategies for MRgFUS include radiosensitization, sonodynamic therapy, histotripsy, and thermal ablation. FUS can also be used to monitor the treatment and progression of gliomas using blood-based liquid biopsy. All these methods are still under preclinical or clinical trials and are described in this review to summarize current knowledge and ongoing trials.

Towards Effective Treatment of Glioblastoma: The Role of Combination Therapies and the Potential of Phytotherapy and Micotherapy.

Glioblastoma multiforme (GBM) is one of the most aggressive and difficult-to-treat brain tumors, with a poor prognosis due to its high resistance to conventional therapies. Current treatment options, including surgical resection, radiotherapy, and chemotherapy, have limited effectiveness in improving long-term survival. Despite the emergence of new therapies, monotherapy approaches have not shown significant improvements, highlighting the need for innovative therapeutic strategies. Combination therapies appear to be the most promising solution, as they target multiple molecular pathways involved in GBM progression. One area of growing interest is the incorporation of phytotherapy and micotherapy as complementary treatments, which offer potential benefits due to their anti-tumor, anti-inflammatory, and immunomodulatory properties. This review examines the current challenges in GBM treatment, discusses the potential of combination therapies, and highlights the promising role of phytotherapy and micotherapy as integrative therapeutic options for GBM management.

The anti-glypican 1 AT101 antibody as targeting agent to effectively deliver chitosan nanobubbles to glioblastoma cells.

Recently, we developed AT101, an IgM-class mouse monoclonal antibody directed against glypican-1 (GPC1), a proteoglycan that can be considered as useful target for glioblastoma multiforme (GBM) treatment being specifically and highly expressed on GBM cell surface. Here, we proposed the use of AT101 as targeting agent in a drug delivery nanoplatfom to effectively deliver chitosan nanobubbles (NBs) for GBM treatment. Chitosan NBs were prepared and conjugated with AT101 or left unconjugated as control. The ability of AT101 to bind the GPC1 protein was demonstrated by flow cytometry and immunofluorescence analysis in the "GBM-like" GPC1-expressing cell lines U-87 MG and T98G. AT101 was shown to bind GPC1-expressing GBM tumor samples by immunofluorescence. In-vivo experiments in the U-87 MG xenograft model showed that AT101 was able to bind GPC1 on cell surface and accumulate in U-87 MG tumor masses (p = 0.0002 respect to control). Moreover, in-vivo experiments showed that AT101 is able to target GPC1 when conjugated to chitosan NBs, thus increasing their specific deliver to GPC1-expressing cells of U-87 MG tumor, as compared to chitosan NBs not conjugated to AT101 (p = 0.02). AT101 is an useful targeting agent for the development of drug delivery nanoplatforms for GBM treatment.

Immunomodulatory Interventions Based on a Bioinformatics Study of TLR2 in Glioblastoma Multiforme.

One of the most malignant types of tumors with a remarkable ability of recurrence rate and aggressiveness is glioblastoma multiforme(GBM). Anyway, according to the restricted remedies accessible for the treatment of this serious tumor, there is no confident and stable therapeutic strategy. Notably, bioinformatics analysis can detect many effective genes in the diagnosis and treatment of GBM. Using large-scale data analysis and bioinformatics, we examined TLR2's role in GBM. We analyzed gene expression datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) to recognize disparately expressed diverse genes (DEGs) associated with TLR2. A protein-protein interaction (PPI) network was constructed to reveal potential molecular partners and functional enrichment analysis elucidated biological activities. In this account, the correlation and association between TLR2 expression and the infiltration of immune cells within the tumor microenvironment were investigated. Results: Our analysis demonstrated significant differential gene expression patterns in GBM, especially TLR2. The PPI network highlighted interactions with key proteins in pathways related to proliferation, invasion, immune evasion, and angiogenesis. Functional enrichment analysis indicated TLR2's involvement in critical signaling processes, including toll-like receptor signaling. Interestingly, TLR2 expression was strongly associated with the infiltration of immune cells, proposing its performance and function in the tumor microenvironment. Understanding TLR2's functions in glioblastoma and other cancers is vital for developing targeted therapies and immunomodulatory interventions, potentially improving clinical outcomes for patients facing these formidable diseases. Further validation and functional studies are needed to confirm TLR2's role in cancer and expand the prospects for combination therapies.

Molecular design of ternary copolymers with high photothermal performance in the near-infrared window for effective treatment of gliomas in vivo.

Photothermal therapy (PTT) is a promising approach for treating glioblastoma multiforme (GBM) with minimal invasiveness and favorable outcomes. Conjugated polymers as photothermal agents offer stability, biocompatibility, and adjustable absorption capacity. However, existing polymers face limitations in achieving high photothermal conversion efficiency and strong absorbance in the near-infrared (NIR) region, posing a risk of damaging healthy tissues surrounding GBM during precise PTT. Herein, a molecular design strategy was developed to create a series of ternary copolymers by incorporating various π-conjugated molecules into both the main chain and side chain. Through this approach, PDTT-253, with rational molar contents of three units and a relatively minor twisted architecture between donors and π-bridges, demonstrated strong NIR absorbance and high PCE of 85.1 % at 808 nm. Furthermore, PDTT-253 nanoparticles exhibited exceptional photothermal stability, photostability, and prolonged storage validity period. In vitro studies revealed high biocompatibility and strong NIR photothermal killing efficacy of PDTT-253 NPs when incubated with U87 cells. Following the injection of PDTT-253 NPs into U87 glioma-bearing mice, a single 808 nm laser irradiation treatment resulted in the inhibition of glioma growth, with the ablated glioma being entirely detached from the surrounding normal tissue after PTT treatment, leading to a comprehensive cure. These results suggest that photostable and biocompatible ternary copolymer nanoparticles based on PDTT-253 show promise for PTT therapy in brain tumors through in situ injection and NIR irradiation. STATEMENT OF SIGNIFICANCE: A molecular design strategy was developed to create a series of ternary copolymers by incorporating various π-conjugated molecules into the conjugated skeleton. Through this approach, PDTT-253, with rational molar contents of three units and a relatively minor twisted architecture between donors and π-bridges, demonstrated enhanced near-infrared (NIR) absorbance and photothermal conversion efficiency of 85.1 % at 808 nm. Furthermore, PDTT-253 nanoparticles exhibited exceptional photothermal stability, high biocompatibility, and strong NIR photothermal killing efficacy against U87 cells. Following the injection of PDTT-253 NPs into U87 glioma-bearing mice, a single 808 nm laser irradiation treatment resulted in the inhibition of glioma growth, with the ablated glioma being entirely detached from the surrounding normal tissue after photothermal therapy treatment, leading to a comprehensive cure.

Glioma-Derived Exosomes and Their Application as Drug Nanoparticles.

Glioblastoma Multiforme (GBM) is the most aggressive primary tumor of the Central Nervous System (CNS) with a low survival rate. The malignancy of GBM is sustained by a bidirectional crosstalk between tumor cells and the Tumor Microenvironment (TME). This mechanism of intercellular communication is mediated, at least in part, by the release of exosomes. Glioma-Derived Exosomes (GDEs) work, indeed, as potent signaling particles promoting the progression of brain tumors by inducing tumor proliferation, invasion, migration, angiogenesis and resistance to chemotherapy or radiation. Given their nanoscale size, exosomes can cross the blood-brain barrier (BBB), thus becoming not only a promising biomarker to predict diagnosis and prognosis but also a therapeutic target to treat GBM. In this review, we describe the structural and functional characteristics of exosomes and their involvement in GBM development, diagnosis, prognosis and treatment. In addition, we discuss how exosomes can be modified to be used as a therapeutic target/drug delivery system for clinical applications.

Bevacizumab: The future of chronic subdural hematoma.

Bevacizumab (BCZ), commercially known as Avastin, is a monoclonal antibody that targets vascular endothelial growth factor (VEGF). Initially recognized as a breakthrough in oncology, it has since gained FDA approval for various ocular conditions and more recently, for the treatment of glioblastoma multiforme (GBM). Bevacizumab's ability to inhibit excessive neovascularization suggests it may have a potential role in treating chronic subdural hematomas (cSDH). Recent studies have shown that the pathophysiology of cSDH is more complex than previously understood, with VEGF concentrations in subdural fluid significantly exceeding those in serum, contributing to the high recurrence rates. Intra-arterial administration of bevacizumab has shown promising results in recent case series against chronic subdural hematoma, and may be a viable alternative to middle meningeal artery embolization. If successful, this treatment could significantly decrease the rate of recurrence and result in lower rates of severe neurological complications such as visual loss. This literature review explores the connection between bevacizumab and cSDH, focusing on the pharmacological, safety, and delivery aspects of this approach while summarizing the current evidence supporting its use.

A Methodical Review of Intranasal Delivery of Nanocarriers for the Treatment of Glioblastoma: An Emerging Therapeutic Option

Glioblastoma multiforme (GBM) is responsible for about half of all primary malignant tumors in the central nervous system (CNS). Nanotechnology and nanocarrier-based drug delivery may prove to be an asset in the ongoing fight against the difficulties associated with treating GBM. Obstacles to effective drug delivery in GBM treatment include prolonged blood circulation, sufficient BBB transit, effective internalization, and controlled drug release within GBM cells. By virtue of the non-specific and non-targeted character of anti-tumor medicines, the efficiency of medication delivery to gliomas is still impoverished. Glioma diagnosis and therapy have undergone a paradigm change solely because of nanotechnology. The highly invasive nature of this malignant glioma makes surgical resection a challenging procedure, and the current approved standard of care—follow-up radiation therapy with concurrent temozolomide (TMZ)—will only prolong the lifespan of patients by a few months. Drug delivery nanosystems (DDNSs) have garnered attention in the treatment of cancer, particularly gastrointestinal cancer, according to recent studies. This is because DDNPs have proven to be effective substitutes for conventional formulations currently on the market, in addition to optimizing the delivery of drugs to neoplastic cells, ameliorating the profile of toxicity and unfavorable effects, and reducing the overall harmful effects of formulations that include antineoplastic agents. Specifically, nanocarriers have proven to have an exceptional ability to get over the difficulties to achieve drug accumulation in the brain without going through the system delivering by IN route. Pre-clinical research on polymeric nanocarriers for treating GBM is ongoing, with few drug delivery systems entering clinical trials. This study examines nanoparticle forms, and brain tumor statistics, and summaries the diagnosis and treatment of GBM utilizing nanotechnology.