Nanoparticle-Based Combinational Strategies for Overcoming the Blood-Brain Barrier and Blood-Tumor Barrier

International Journal of Nanomedicine, Год журнала: 2024, Номер Volume 19, С. 2529 - 2552

Опубликована: Март 1, 2024

Abstract: The blood-brain barrier (BBB) and blood-tumor (BTB) pose substantial challenges to efficacious drug delivery for glioblastoma multiforme (GBM), a primary brain tumor with poor prognosis. Nanoparticle-based combinational strategies have emerged as promising modalities overcome these barriers enhance penetration into the parenchyma. This review discusses various nanoparticle-based combinatorial approaches that combine nanoparticles cell-based delivery, viral focused ultrasound, magnetic field, intranasal permeability across BBB BTB. Cell-based involves using engineered cells carriers nanoparticles, taking advantage of their intrinsic migratory homing capabilities facilitate transport therapeutic payloads Viral uses vectors deliver genes or specific within GBM microenvironment. Focused coupled microbubbles can temporarily disrupt increase permeability. Magnetic field-guided exploits targeted under an external field. Intranasal offers minimally invasive avenue bypass agents directly via olfactory trigeminal pathways. By combining strategies, synergistic effects efficiency, improve efficacy, reduce off-target effects. Future research should focus on optimizing nanoparticle design, exploring new combination advancing preclinical clinical investigations promote translation therapies GBM. Keywords: glioblastoma, barrier, nanoparticle, strategy, ultrasound-wave,

Язык: Английский

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Advanced drug delivery platforms target cancer stem cells

Asian Journal of Pharmaceutical Sciences, Год журнала: 2025, Номер unknown, С. 101036 - 101036

Опубликована: Фев. 1, 2025

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Glioblastoma: Clinical Presentation, Multidisciplinary Management, and Long-Term Outcomes

Cancers, Год журнала: 2025, Номер 17(1), С. 146 - 146

Опубликована: Янв. 5, 2025

Glioblastoma, the most common and aggressive primary brain tumor in adults, presents a formidable challenge due to its rapid progression, treatment resistance, poor survival outcomes. Standard care typically involves maximal safe surgical resection, followed by fractionated external beam radiation therapy concurrent temozolomide chemotherapy. Despite these interventions, median remains approximately 12–15 months, with five-year rate below 10%. Prognosis is influenced factors such as patient age, molecular characteristics, extent of resection. Patients IDH-mutant tumors or methylated MGMT promoters generally have improved survival, while recurrent glioblastoma associated only six therapies cases are often palliative. Innovative treatments, including TTFields, add incremental benefits, extending around 20.9 months for eligible patients. Symptom management—addressing seizures, headaches, neurological deficits—alongside psychological support patients caregivers essential enhance quality life. Emerging targeted immunotherapies, though still limited efficacy, show promise part an evolving landscape. Continued research clinical trials remain crucial developing more effective treatments. This multidisciplinary approach, incorporating diagnostics, personalized therapy, supportive care, aims improve outcomes provides hopeful foundation advancing management.

Язык: Английский

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Cytotoxic effect of diferuloylmethane, a derivative of turmeric on different human glioblastoma cell lines

Cellular Molecular and Biomedical Reports, Год журнала: 2021, Номер 1(1), С. 14 - 22

Опубликована: Июнь 1, 2021

Glioblastoma is a fatal brain tumor, and the standard treatment for this cancer surgical removal of tumor followed by chemotherapy with temozolomide radiotherapy. Because has many side effects, use compounds extracted from natural herbs, due to fewer can be good alternative or supplement chemical drugs in treatment. In study, curcumin (diferuloylmethane), known as main active ingredient turmeric, was used evaluate itscytotoxicity on four human glioblastoma cell lines (U373, U251, D54, T98G). Among these lines, U373 resistance, T98G photodynamic resistance. These were treated increasing concentrations diferuloylmethane. Survival percentage assessed MTT assay trypan blue staining method rate death confirm results assay. The showed that diferuloylmethane cytotoxic effect lines. This higher high U251 D54 than U373. Therefore, according current study further studies, (diferuloylmethane) considered an effective complementary glioblastoma.

Язык: Английский

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New Directions in the Therapy of Glioblastoma

Cancers, Год журнала: 2022, Номер 14(21), С. 5377 - 5377

Опубликована: Окт. 31, 2022

Glioblastoma is the most common histologic type of all gliomas and contributes to 57.3% cases. Despite standard management based on surgical resection radiotherapy, it related poor outcome, with a 5-year relative survival rate below 6.9%. In order improve overall outcome for patients, new therapeutic strategies are needed. Herein, we describe current state knowledge novel targeted therapies in glioblastoma. Based recent studies, compared treatment efficacy measured by progression-free patients treated selected potential antitumor drugs. The results application analyzed inhibitors highly variable despite encouraging conclusions previous preclinical studies. This paper focused drugs that target major glioblastoma kinases. As far, some BRAF favorable. Vemurafenib demonstrated long-term clinical trials while combination dabrafenib trametinib improves PFS both vemurafenib alone. There no evidence any MEK inhibitor effective monotherapy. According knowledge, inhibition more advantageous than Moreover, mTOR (especially paxalisib) may be considered particularly important group. Everolimus partial response significant proportion when combined bevacizumab, however its actual role unclear. Neither nintedanib nor pemigatinib were efficient GBM. Among anti-VEGF drugs, bevacizumab monotherapy was well-tolerated option, significantly associated anti-GBM activity recurrent aflibercept pazopanib has not been demonstrated. Apatinib proven tolerable single trial, but research Lenvatinib under trial. Finally, promising from study regorafenib confirmed ongoing randomized AGILE studies conducted so far have provided relatively wide range which at least well tolerated trials. comprehensive understanding molecular biology promises further outcomes patients.

Язык: Английский

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Lipid Metabolism in Glioblastoma: From De Novo Synthesis to Storage

Biomedicines, Год журнала: 2022, Номер 10(8), С. 1943 - 1943

Опубликована: Авг. 11, 2022

Glioblastoma (GBM) is the most lethal primary brain tumor. With limited therapeutic options, novel therapies are desperately needed. Recent studies have shown that GBM acquires large amounts of lipids for rapid growth through activation sterol regulatory element-binding protein 1 (SREBP-1), a master transcription factor regulates fatty acid and cholesterol synthesis, uptake. Interestingly, cells divert substantial quantities into lipid droplets (LDs), specific storage organelle neutral lipids, to prevent lipotoxicity by increasing expression diacylglycerol acyltransferase (DGAT1) sterol-O-acyltransferase (SOAT1), which convert excess acids triacylglycerol cholesteryl esters, respectively. In this review, we will summarize recent progress on our understanding metabolism regulation in promote tumor discuss strategies specifically induce disrupting storage, promising new avenue treating GBM.

Язык: Английский

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Nanotechnology meets glioblastoma multiforme: Emerging therapeutic strategies

Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology, Год журнала: 2022, Номер 15(1)

Опубликована: Авг. 12, 2022

Glioblastoma multiforme (GBM) represents the most common and fatal form of primary invasive brain tumors as it affects a great number patients each year has median overall survival approximately 14.6 months after diagnosis. Despite intensive treatment, almost all with GBM experience recurrence, their 5-year rate is 5%. At present, main clinical treatment strategy includes surgical resection, radiotherapy, chemotherapy. However, tumor heterogeneity, blood-brain barrier, glioma stem cells, DNA damage repair mechanisms hinder efficient treatment. The emergence nanometer-scale diagnostic therapeutic approaches in cancer medicine due to establishment nanotechnology provides novel promising tools that will allow us overcome these difficulties. This review summarizes application recent progress nanotechnology-based monotherapies (e.g., chemotherapy) combination strategies (chemotherapy-based combined therapy) for describes synergistic enhancement between therapies well current standard therapy its deficiencies. These can reduce individual drug-related toxicities significantly enhance efficiency have recently undergone rapid development. underlying different photodynamic chemodynamic been systematically summarized here an attempt developments identify directions future research. clinically significant insights GBM, which importance. article categorized under: Therapeutic Approaches Drug Discovery > Nanomedicine Oncologic Disease Diagnostic Tools In Vivo Nanodiagnostics Imaging.

Язык: Английский

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Molecular and Circulating Biomarkers in Patients with Glioblastoma

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(13), С. 7474 - 7474

Опубликована: Июль 5, 2022

Glioblastoma is the most aggressive malignant tumor of central nervous system with a low survival rate. The difficulty obtaining this material represents major limitation, making real-time monitoring progression difficult, especially in events recurrence or resistance to treatment. identification characteristic biomarkers indispensable for an accurate diagnosis, rigorous follow-up patients, and development new personalized treatments. Liquid biopsy, as minimally invasive procedure, holds promise regard. purpose paper summarize current literature regarding molecular circulating glioblastoma importance their integration valuable tool improve patient care.

Язык: Английский

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PDIA3P1 promotes Temozolomide resistance in glioblastoma by inhibiting C/EBPβ degradation to facilitate proneural-to-mesenchymal transition

Journal of Experimental & Clinical Cancer Research, Год журнала: 2022, Номер 41(1)

Опубликована: Июль 15, 2022

Resistance to temozolomide (TMZ) is a major obstacle preventing glioblastoma (GBM) recurrence after surgery. Although long noncoding RNAs (lncRNAs) play variety of roles in GBM, the lncRNAs that regulate TMZ resistance have not yet been clearly elucidated. This study aims identify may affect treatment sensitivity and explore novel therapeutic strategies overcome GBM.LncRNAs associated with were identified using Cancer Cell Line Encyclopedia (CCLE) Genomics Drug Sensitivity (GDSC) datasets. Quantitative real-time PCR (qRT-PCR) was used determine expression PDIA3P1 TMZ-resistant TMZ-sensitive GBM cell lines. Both gain-of-function loss-of-function studies assess effects on vitro vivo assays. Glioma stem cells (GSCs) effect subtype. The hypothesis promotes proneural-to-mesenchymal transition (PMT) established bioinformatics analysis functional experiments. RNA pull-down immunoprecipitation (RIP) assays performed examine interaction between C/EBPβ. posttranslational modification mechanism C/EBPβ verified ubiquitination coimmunoprecipitation (co-IP) CompuSyn leveraged calculate combination index (CI), antitumor combined nefllamapimod (NEF) validated both vivo.We lncRNA, PDIA3P1, which upregulated Overexpression promoted acquisition resistance, whereas knockdown restored sensitivity. MES-GBM, PMT progression GSCs, caused GBMs be more resistant treatment. Mechanistically, disrupted C/EBPβ-MDM2 complex stabilized protein by MDM2-mediated ubiquitination. Expression time- concentration-dependent manner response treatment, TMZ-induced upregulation mediated p38α-MAPK signaling pathway. NEF small molecule drug specifically targets p38α excellent blood-brain barrier (BBB) permeability. blocked TMZ-responsive produced synergistic when at specific concentrations. exhibited vivo.PDIA3P1 stabilizing C/EBPβ, reducing inhibits upregulation, provides better effects.

Язык: Английский

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Glioblastoma research on zebrafish xenograft models: a systematic review

Clinical & Translational Oncology, Год журнала: 2023, Номер 26(2), С. 311 - 325

Опубликована: Июль 3, 2023

Abstract Glioblastoma (GBM) constitutes the most common primary brain tumor in adults. The challenges GBM therapeutics have shed light on zebrafish used as a promising animal model for preclinical xenograft studies without standardized methodology. This systematic review aims to summarize advances xenografting, compare research protocols pinpoint advantages and underlying limitations, designate predominant xenografting parameters. Based PRISMA checklist, we systematically searched PubMed, Scopus, ZFIN using keywords “glioblastoma,” “xenotransplantation,” “zebrafish” papers published from 2005 2022, available English. 46 articles meeting criteria were examined strain, cancer cell line, labeling technique, injected number, time site of injection, maintenance temperature. Our designated that AB wild-type zebrafish, Casper transparent mutants, transgenic Tg(fli1:EGFP), or crossbreeding these predominate among strains. Orthotopic transplantation is more commonly employed. A number 50–100 cells at 48 h post-fertilization high density low infusion volume considered an effective approach. U87 are angiogenesis studies, U251 proliferation patient-derived (PDX) achieve clinical relevance. Gradual acclimatization 32–33 °C can partly address temperature differential between cells. Zebrafish models constitute valuable tools with relevance regarding PDX. requires modification based objective each team. Automation further optimization protocol parameters could scale up anticancer drug trials.

Язык: Английский

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