Journal of Neuro-Oncology, Journal Year: 2024, Volume and Issue: 171(3), P. 495 - 530
Published: Nov. 13, 2024
Language: Английский
Science, Journal Year: 2024, Volume and Issue: 385(6714)
Published: Sept. 12, 2024
Focused ultrasound is a platform technology capable of eliciting wide range biological responses with high spatial precision deep within the body. Although focused already in clinical use for focal thermal ablation tissue, there has been recent growth development and translation ultrasound-mediated nonthermal therapies. These approaches exploit physical forces to produce dependent on exposure conditions. This review discusses advances four application areas that have seen particular immense potential: brain drug delivery, neuromodulation, tissue destruction, endogenous immune system activation. Owing maturation transcranial technology, major target organ; however, indications outside are also discussed.
Language: Английский
Citations
15
Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 10, 2024
While immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized the clinical management of various malignancies, a large fraction patients are refractory to ICIs employed as standalone therapeutics, necessitating development combinatorial treatment strategies. Immunogenic cell death (ICD) inducers have attracted considerable interest partners for ICIs, at least in part owing their ability initiate tumor-targeting adaptive response. However, compared either approach alone, regimens involving ICD and not always shown superior activity. Here, we discuss accumulating evidence on therapeutic interactions between oncological settings, identify key factors that may explain discrepancies preclinical findings, propose strategies address existing challenges increase efficacy these combinations cancer.
Language: Английский
Citations
11
ACS Nano, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 3, 2025
The blood–brain barrier (BBB) remains a major obstacle for effective delivery of therapeutics to treat central nervous system (CNS) disorders. Although transferrin receptor (TfR)-mediated transcytosis is widely employed brain drug delivery, the inefficient release therapeutic payload hinders their efficacy from crossing BBB. Here, we developed pH-responsive anti-polyethylene glycol (PEG) × anti-TfR bispecific antibody (pH-PEG engagerTfR) that can complex with PEGylated nanomedicine at physiological pH trigger TfR-mediated in microvascular endothelial cells, while rapidly dissociating acidic endosomes efficient cross pH-PEG engagerTfR significantly increased accumulation mouse compared wild-type PEG (WT-PEG engagerTfR). engagerTfR-decorated liposomal doxorubicin exhibited an enhanced antitumor effect and extended survival human glioblastoma (GBM) orthotopic xenograft mice model. Conditional during BBB-related receptor-mediated by promising CNS
Language: Английский
Citations
1
Biomaterials, Journal Year: 2025, Volume and Issue: 319, P. 123180 - 123180
Published: Feb. 13, 2025
Language: Английский
Citations
1
International Journal of Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown, P. 125612 - 125612
Published: April 1, 2025
The immunosuppressive tumor immune microenvironment (TIME) renders glioblastoma (GBM) refractory to current chemo-immunotherapeutics. We sought explore a novel approach for local GBM-associated TIME immunomodulation based on synergistic combination of the repurposed chemotherapeutic drugs doxorubicin (DOX), which acts induce immunogenic cell death (ICD) and gemcitabine (GEM), depletes myeloid-derived suppressor cells (MDSCs). conjugated DOX GEM hyaluronic acid (HA) improve efficacy, given this polymer's ability target CD44 are overexpressed cancer cells. HA-DOX HA-GEM polymer-drug conjugates provided cytotoxic effects maintained ICD-related properties in GBM compared free drugs. also reverted orthotopic GL261 tumor-bearing mice by selectively depleting MDSCs reprogramming M2-like macrophages towards pro-inflammatory M1-like state, resulting controlled growth. Local delivery increased median survival growth an SB28-GBM mouse model. These findings highlight potential repurposing clinically applicable chemotherapeutics context treatments strategies unresectable GBM, may open new avenues developing innovative therapies.
Language: Английский
Citations
1
Neuro-Oncology, Journal Year: 2024, Volume and Issue: 26(11), P. 2044 - 2060
Published: July 19, 2024
Abstract Background Glioblastoma is a highly aggressive brain cancer that resistant to conventional immunotherapy strategies. Botensilimab, an Fc-enhanced anti-CTLA-4 antibody (FcE-aCTLA-4), has shown durable activity in “cold” and immunotherapy-refractory cancers. Methods We evaluated the efficacy immune microenvironment phenotype of mouse analogue FcE-aCTLA-4 treatment-refractory preclinical models glioblastoma, both as monotherapy combination with doxorubicin delivered via low-intensity pulsed ultrasound microbubbles (LIPU/MB). Additionally, we studied 4 glioblastoma patients treated doxorubicin, anti-PD-1 concomitant LIPU/MB investigate novel effect modulating FcγR expressions tumor-associated macrophages/microglia (TAMs). Results demonstrated high-affinity binding FcγRIV, ortholog human FcγRIIIA, which was expressed TAMs most robustly at diagnosis. Notably, FcE-aCTLA-4-mediated selective depletion intratumoral regulatory T cells (Tregs) TAM-mediated phagocytosis, while sparing peripheral Tregs. Doxorubicin, chemotherapeutic drug immunomodulatory functions, found upregulate FcγRIIIA on who received LIPU/MB. In murine immunotherapy-resistant gliomas, combinatorial regimen FcE-aCTLA-4, anti-PD-1, LIPU/MB, achieved 90% cure rate, associated robust infiltration activated CD8+ establishment immunological memory evidenced by rejection upon tumor rechallenge. Conclusions Our findings demonstrate promotes anti-tumor effects gliomas significantly enhanced when combined are currently investigating this combinatory strategy clinical trial (clinicaltrials.gov NCT05864534).
Language: Английский
Citations
7
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9714 - 9714
Published: Sept. 8, 2024
Glioblastoma (GBM) is one of the most aggressive malignant tumors brain. We queried PubMed for articles about molecular predictor markers in GBM. This scoping review aims to analyze important outcome predictors patients with GBM and compare these factors terms absolute months survival benefit percentages. Performing a gross total resection undergoing optimal chemo- radiotherapy provides significant overall compared those who received subtotal or partial resection. However, IDH-Wildtype GBMs, IDH-Mutant 1/2 GBMs have an increased survival. MGMT promoter methylation status another strong In reviewed literature, methylated lived approximately 50% 90% longer than unmethylated gene promoter. Moreover, KPS quality life, demonstrating that we should refrain from surgery brain areas. As new therapies (such as TTFs) emerge, are optimistic median will increase, even GBMs. conclusion, profiles stronger extent neurosurgical
Language: Английский
Citations
4
medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 20, 2025
Abstract Background The blood-brain barrier (BBB) impedes the passage of most circulating drugs into brain. Low-intensity pulsed ultrasound with microbubbles (LIPU/MB) transiently opens BBB, improving parenchymal drug penetration. Parenchymal permanence upon short-lived BBB opening is unknown. We compared temozolomide, carboplatin, and fluorescein, investigated effect LIPU/MB on concentration carboplatin fluorescein. Methods analyzed four patients who underwent intraoperative intravenous administration fluorescein in NCT04528680 clinical trial. Microdialysis catheters were implanted sonicated non-sonicated brain measured levels over 24 hours. Published data from a microdialysis study temozolomide without used for comparison. Results led to sustained elevated concentrations, achieving 3.1-fold increase brain-to-plasma AUC (P = 0.03). Compared brain, had higher concentrations 11 hours, 5 Drug exceeded their plasma at 21 hours 7 respectively. In half-life was longest (13.6 ± 11.0 hours), followed by (5.1 1.9 hours) (2.9 1.6 hours). Sonication did not affect half-life. Conclusion Following LIPU/MB, BBB-impermeable exhibit surpassing levels, highlighting bi-directional restriction BBB. Future studies are warranted explore trapping efficacy exposure cytotoxic treatment brain-infiltrating tumors.
Language: Английский
Citations
0
Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)
Published: Feb. 24, 2025
Focused ultrasound (FUS) has emerged as a promising technique for temporarily disrupting the blood-brain barrier (BBB) and blood-tumor (BTB) to enhance delivery of therapeutic agents. Despite its potential, optimizing FUS maximize drug while minimizing adverse effects remains significant challenge. In this study, we evaluated novel protocol that incorporates additional stimulation without microbubbles (MBs) ("FUS protocol") prior conventional BBB disruption with MBs ("BBBD in rat brain tumor model (n = 35). This approach aimed validate effectiveness enhancing BBB/BTB facilitating doxorubicin delivery. T1-weighted contrast-enhanced dynamic (DCE) MRI demonstrated increases signal intensity permeability (Ktrans) region under "FUS + BBBD protocol", 2.65-fold 2.08-fold increases, respectively, compared non-sonicated contralateral region. These values were also elevated "BBBD protocol" by 1.45-fold 1.25-fold, respectively. Furthermore, targeted increased 1.91-fold 1.44-fold increase using protocol". offers promising, cost-effective strategy tumors. While further studies are required assess applicability different chemotherapeutics types, it holds potential improving treatment both preclinical clinical settings.
Language: Английский
Citations
0
International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 306, P. 141737 - 141737
Published: March 4, 2025
Language: Английский
Citations
0