Macrophage Membrane-Camouflaged Responsive Polymer Nanogels Enable Magnetic Resonance Imaging-Guided Chemotherapy/Chemodynamic Therapy of Orthotopic Glioma

ACS Nano, Год журнала: 2021, Номер 15(12), С. 20377 - 20390

Опубликована: Дек. 3, 2021

Development of innovative nanomedicine formulations to traverse the blood–brain barrier (BBB) for effective theranostics glioma remains a great challenge. Herein, we report creation macrophage membrane-camouflaged multifunctional polymer nanogels coloaded with manganese dioxide (MnO2) and cisplatin magnetic resonance (MR) imaging-guided chemotherapy/chemodynamic therapy (CDT) orthotopic glioma. Redox-responsive poly(N-vinylcaprolactam) (PVCL) (NGs) formed via precipitation polymerization were in situ loaded MnO2 physically encapsulated have mean size 106.3 nm coated membranes good colloidal stability. The generated hybrid NGs display dual pH- redox-responsive Mn(II) release profiles can deplete glutathione (GSH) rich tumor microenvironment through reaction disulfide-containing cross-linkers within MnO2. thus created enables enhanced CDT Fenton-like T1-weighted MR imaging, while not only exerts its chemotherapy effect but also promotes reactive oxygen species generation enhance efficacy. Importantly, membrane coating rendered prolonged blood circulation time ability BBB specific targeted chemotherapy/CDT Our study demonstrates promising self-adaptive cooperative NG-based platform highly efficient glioma, which may be extended tackle other difficult cancer types.

Язык: Английский

---

Wnt and PI3K/Akt/mTOR Survival Pathways as Therapeutic Targets in Glioblastoma

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(3), С. 1353 - 1353

Опубликована: Янв. 25, 2022

Glioblastoma (GBM) is a devastating type of brain tumor, and current therapeutic treatments, including surgery, chemotherapy, radiation, are palliative at best. The design effective targeted chemotherapeutic strategies for the treatment GBM require thorough analysis specific signaling pathways to identify those serving as drivers progression invasion. Wnt/β-catenin PI3K/Akt/mTOR (PAM) key regulators important biological functions that include cell proliferation, epithelial–mesenchymal transition (EMT), metabolism, angiogenesis. Targeting regulatory components PAM has potential disrupt critical tumor achieve advancements in alternative enhance survival rate patients. In this review, we emphasize importance invasion into tissue explore their targets.

Язык: Английский

---

Mechanisms of Resistance and Current Treatment Options for Glioblastoma Multiforme (GBM)

Cancers, Год журнала: 2023, Номер 15(7), С. 2116 - 2116

Опубликована: Апрель 1, 2023

Glioblastoma multiforme (GBM) is a highly aggressive form of brain cancer that difficult to treat due its resistance both radiation and chemotherapy. This largely the unique biology GBM cells, which can evade effects conventional treatments through mechanisms such as increased cell death rapid regeneration cancerous cells. Additionally, blood–brain barrier makes it for chemotherapy drugs reach leading reduced effectiveness. Despite these challenges, there are several treatment options available GBM. The standard care newly diagnosed patients involves surgical resection followed by concurrent chemoradiotherapy adjuvant Emerging include immunotherapy, checkpoint inhibitors, targeted therapies, bevacizumab, attempt attack specific vulnerabilities in Another promising approach use tumor-treating fields, type electric field therapy has been shown slow growth Clinical trials ongoing evaluate safety efficacy other innovative GBM, intending improve with outcomes patients.

Язык: Английский

---

Signaling pathways and therapeutic approaches in glioblastoma multiforme (Review)

International Journal of Oncology, Год журнала: 2022, Номер 60(6)

Опубликована: Апрель 19, 2022

Glioblastoma multiforme (GBM) is the most aggressive type of primary brain tumor and associated with a poor clinical prognosis. Despite progress in understanding molecular genetic changes that promote tumorigenesis, effective treatment options are limited. The present review intended to identify summarize major signaling pathways abnormalities involved pathogenesis GBM, as well therapies target these pathways. remains difficult treat tumor; however, last two decades, significant improvements GBM biology have enabled advances available therapeutics. Significant genomic events pathway disruptions (NF‑κB, Wnt, PI3K/AKT/mTOR) formation were discussed. Current therapeutic may only marginally prolong survival current standard therapy cures small fraction patients. As result, there an unmet requirement for further study into processes glioblastoma discovery novel targets implicated evolution glioblastoma.

Язык: Английский

---

Functionalized Nanomaterials Capable of Crossing the Blood–Brain Barrier

ACS Nano, Год журнала: 2024, Номер 18(3), С. 1820 - 1845

Опубликована: Янв. 9, 2024

The blood–brain barrier (BBB) is a specialized semipermeable structure that highly regulates exchanges between the central nervous system parenchyma and blood vessels. Thus, BBB also prevents passage of various forms therapeutic agents, nanocarriers, their cargos. Recently, many multidisciplinary studies focus on developing cargo-loaded nanoparticles (NPs) to overcome these challenges, which are emerging as safe effective vehicles in neurotheranostics. In this Review, first we introduce anatomical physiological functions BBB. Second, present endogenous exogenous transport mechanisms by NPs cross We report nanomaterials, carriers, cargos, with detailed uptake permeability characteristics. Third, describe effect regulating size, shape, charge, surface ligands affect permeability, can be exploited enhance promote classify typical functionalized nanomaterials developed for crossing. Fourth, provide comprehensive review recent progress functional polymeric applications multimodal bioimaging, therapeutics, drug delivery. Finally, conclude discussing existing directions, future perspectives employing

Язык: Английский

---

Nanosensitizers for sonodynamic therapy for glioblastoma multiforme: current progress and future perspectives

Military Medical Research, Год журнала: 2022, Номер 9(1)

Опубликована: Июнь 9, 2022

Abstract Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor, and it associated with poor prognosis. Its characteristics of being highly invasive undergoing heterogeneous genetic mutation, as well presence blood–brain barrier (BBB), have reduced efficacy GBM treatment. The emergence a novel therapeutic method, namely, sonodynamic therapy (SDT), provides promising strategy for eradicating tumors via activated sonosensitizers coupled low-intensity ultrasound. SDT can provide tumor killing effects deep-seated tumors, such tumors. However, conventional cannot effectively reach region kill additional cells, especially cells. Efforts should be made to develop method help agents pass through BBB accumulate in With development multifunctional nanosensitizers newly emerging combination strategies, ability selectivity greatly improved are accompanied fewer side effects. In this review, we systematically summarize findings previous studies on GBM, focus recent developments directions future research.

Язык: Английский

---

Advances in Glioblastoma Therapy: An Update on Current Approaches

Brain Sciences, Год журнала: 2023, Номер 13(11), С. 1536 - 1536

Опубликована: Окт. 31, 2023

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

Язык: Английский

---

Glioblastoma Therapy: Past, Present and Future

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(5), С. 2529 - 2529

Опубликована: Фев. 21, 2024

Glioblastoma (GB) stands out as the most prevalent and lethal form of brain cancer. Although great efforts have been made by clinicians researchers, no significant improvement in survival has achieved since Stupp protocol became standard care (SOC) 2005. Despite multimodality treatments, recurrence is almost universal with rates under 2 years after diagnosis. Here, we discuss recent progress our understanding GB pathophysiology, particular, importance glioma stem cells (GSCs), tumor microenvironment conditions, epigenetic mechanisms involved growth, aggressiveness recurrence. The discussion on therapeutic strategies first covers SOC treatment targeted therapies that shown to interfere different signaling pathways (pRB/CDK4/RB1/P16

Язык: Английский

---

Glioblastoma Multiforme: The Latest Diagnostics and Treatment Techniques

Pharmacology, Год журнала: 2023, Номер 108(5), С. 423 - 431

Опубликована: Янв. 1, 2023

Background: Glioblastoma multiforme (GBM) is a WHO grade 4 glioma and the most common malignant primary brain tumour. Recently, there has been outstanding progress in treatment of GBM. In addition to newest form GBM removal using fluorescence, three-dimensional (3D) imaging, tomoradiotherapy, moderate electro-hyperthermia, adjuvant temozolomide (post-operative chemotherapy), new developments have made fields immunology, molecular biology, virotherapy. An unusual modern created, especially for stage GBM, latest therapeutic techniques, including immunotherapy Modern oncological medicine producing extraordinary progressive methods. Oncological therapy includes individual analysis properties tumour targeted small-molecule inhibitors. Individualised covers entire patient (tumour host) context immunotherapy. example individualised multimodal (IMI), which relies on immunological tumour-host interactions. addition, IMI based concept oncolytic virus-induced immunogenic cell death. Summary: this review, we outline current knowledge various available options used both traditional strategy therapies, such as tomotherapy, virotherapy, are promising strategies with potential improve prognosis patients Key Messages: This therapy, combined virotherapy (oncolytic viruses cancer vaccines), displaying encouraging signs combating Additionally, 3D imaging compared conventional two-dimensional imaging.

Язык: Английский

---

The Role of Curcumin in Cancer: A Focus on the PI3K/Akt Pathway

Cancers, Год журнала: 2024, Номер 16(8), С. 1554 - 1554

Опубликована: Апрель 18, 2024

Cancer is a life-threatening disease and one of the leading causes death worldwide. Despite significant advancements in therapeutic options, most available anti-cancer agents have limited efficacy. In this context, natural compounds with diverse chemical structures been investigated for their multimodal properties. Curcumin polyphenol isolated from rhizomes Curcuma longa has widely studied its anti-inflammatory, anti-oxidant, effects. acts on regulation different aspects cancer development, including initiation, metastasis, angiogenesis, progression. The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) pathway key target therapy, since it implicated proliferation, cell survival. found to inhibit PI3K/Akt tumor cells, primarily via mediators, growth factors, protein kinases, cytokines. This review presents potential curcumin malignancies, such as glioblastoma, prostate breast cancer, head neck cancers, through targeting signaling pathway.

Язык: Английский

---