Modulating the Blood–Brain Barrier: A Comprehensive Review

Whelan, Rory; Hargaden, Gráinne C.; Knox, Andrew J. S.

doi:10.3390/pharmaceutics13111980

Cited by 29 publications

(17 citation statements)

References 259 publications

(313 reference statements)

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“…As mentioned before, CX-4945, combined with gefitinib (an EGFR inhibitor), exerted a strong antiviability effect on glioblastoma cells in vitro [45]. Therefore, further studies utilizing this approach are warranted, possibly including BBB modulators in order to increase levels of kinase inhibitors in glioma tissues in vivo [132].…”

Section: Therapies Combined With Ck2 Inhibitorsmentioning

confidence: 98%

Inhibiting CK2 among Promising Therapeutic Strategies for Gliomas and Several Other Neoplasms

Pucko

Ostrowski

2022

Pharmaceutics

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In gliomas, casein kinase 2 (CK2) plays a dominant role in cell survival and tumour invasiveness and is upregulated in many brain tumours. Among CK2 inhibitors, benzimidazole and isothiourea derivatives hold a dominant position. While targeting glioma tumour cells, they show limited toxicity towards normal cells. Research in recent years has shown that these compounds can be suitable as components of combined therapies with hyperbaric oxygenation. Such a combination increases the susceptibility of glioma tumour cells to cell death via apoptosis. Moreover, researchers planning on using any other antiglioma investigational pharmaceutics may want to consider using these agents in combination with CK2 inhibitors. However, different compounds are not equally effective when in such combination. More research is needed to elucidate the mechanism of treatment and optimize the treatment regimen. In addition, the role of CK2 in gliomagenesis and maintenance seems to have been challenged recently, as some compounds structurally similar to CK2 inhibitors do not inhibit CK2 while still being effective at reducing glioma viability and invasion. Furthermore, some newly developed inhibitors specific for CK2 do not appear to have strong anticancer properties. Further experimental and clinical studies of these inhibitors and combined therapies are warranted.

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Section: Therapies Combined With Ck2 Inhibitorsmentioning

confidence: 98%

Inhibiting CK2 among Promising Therapeutic Strategies for Gliomas and Several Other Neoplasms

Pucko

Ostrowski

2022

Pharmaceutics

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“…Unfortunately, the BBB also obstruct the crossing of various desired medicinal agents into the CNS parenchyma, limiting their potential therapeutic function. [ 190 ]…”

Section: Biomedical Applications Of Dendrimers In the Cns Disease Tre...mentioning

confidence: 99%

“…Unfortunately, the BBB also obstruct the crossing of various desired medicinal agents into the CNS parenchyma, limiting their potential therapeutic function. [190] The CNS therapeutic agents, including high molecular weight drugs, proteins, and genes, have been studied for delivery into the brain via dendrimers carriers. [191,192] Dendrimers conjugates cross the BBB mainly through adsorptivemediated transcytosis (AMT) and receptor-mediated transcytosis (RMT) (Figure 7).…”

Section: Biomedical Applications Of Dendrimers In the Cns Disease Tre...mentioning

confidence: 99%

Polymeric Dendrimers as Nanocarrier Vectors for Neurotheranostics

Zha

Liu

et al. 2022

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immune responses, activating cellular machinery causing cell stress, cytotoxicity, lack of selectivity, increasing the likelihood of replication competence, and the constrained structure of insert-size, which can limit their biological and medical applications. [2][3][4] By contrast, various forms of nonviral vectors are widely developed and applied in biomedical research because of their low immunogenicity, high biocompatibility, simplicity in structural pattern, ease of size adjustment, practicality in designing various active sites, and low cost of production. [5,6] The most widely studied nonviral vectors are liposomes, inorganic nanoparticles, polymers, and dendrimers. [7] Liposomes are small spherical vesicles from cholesterol and phospholipids characterized with the surface that can be modified using glycolipids or sialic acid. Yet, the unmodified forms of liposomes are structurally unstable and could easily be eliminated by means of body circulation. [8] In this situation, stable inorganic nanoparticles, such as calcium phosphate (Ca 3 (PO 4 ) 2 ), gold (Au), iron oxide (Fe 3 O 4 ), and lanthanide-based nanoparticles are widely used, mainly due to their good hydrophilicity and excellent biocompatibility. [9][10][11] Depending on their chemical core composition, these inorganic nanoparticles display different properties and efficiencies. Lately, inorganic nanoparticles have been developed as effective drug delivery systems and used in many diagnostic techniques. [12] In addition, polymers are widely used as nonviral vectors as well. [13][14][15] Polymers are biodegradable nanomaterials with stable and easily modifiable 3D structures. Their uncomplicated synthesis process allows for large-scale production and safe clinical use compared to inorganic nanoparticles. [16] Notably, dendrimers are hyperbranched polymers with a well-defined chemical structure: a core at the center occupied by array of convergent reactive chain-ends and surface that can easily be modified. [17] The chemistry of dendrimers was first described by Buhleier et al. in 1978. [18] In 1985, Tomalia et al. reported a newer kind of dendrimers based on the mixture of amines and amides, termed polyamidoamine (PAMAM) dendrimers. [19] Dendrimers are intermeshed synthetic organic macromolecules with 3D architecture composition and abundant terminal functional groups. They are well-defined monodispersity-sized materials with extraordinary membrane interaction properties Dendrimers are polymers with well-defined 3D branched structures that are vastly utilized in various neurotheranostics and biomedical applications, particularly as nanocarrier vectors. Imaging agents can be loaded into dendrimers to improve the accuracy of diagnostic imaging processes. Likewise, combining pharmaceutical agents and anticancer drugs with dendrimers can enhance their solubility, biocompatibility, and efficiency. Practically, by modifying ligands on the surface of dendrimers, effective therapeutic and diagnostic platforms can be constructed and implemented for target...

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“…Inhibition of Wnt in GBM is also challenging due to the essential roles of this pathway in CNS vascularization and BBB integrity [ 100 ]. During CNS development, neural progenitors-derived Wnt7a and Wnt7b ligands activate canonical Wnt signaling in vascular endothelium, thus promoting vascularization of CNS and formation of BBB [ 164 ]. The same mechanism maintains integrity of BBB in adult brain.…”

Section: Targeting Canonical Wnt/β-catenin Signaling Pathway In Gbmmentioning

confidence: 99%

Current Opportunities for Targeting Dysregulated Neurodevelopmental Signaling Pathways in Glioblastoma

Drakulić

Schwirtlich

Petrović

et al. 2022

Cells

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Glioblastoma (GBM) is the most common and highly lethal type of brain tumor, with poor survival despite advances in understanding its complexity. After current standard therapeutic treatment, including tumor resection, radiotherapy and concomitant chemotherapy with temozolomide, the median overall survival of patients with this type of tumor is less than 15 months. Thus, there is an urgent need for new insights into GBM molecular characteristics and progress in targeted therapy in order to improve clinical outcomes. The literature data revealed that a number of different signaling pathways are dysregulated in GBM. In this review, we intended to summarize and discuss current literature data and therapeutic modalities focused on targeting dysregulated signaling pathways in GBM. A better understanding of opportunities for targeting signaling pathways that influences malignant behavior of GBM cells might open the way for the development of novel GBM-targeted therapies.

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Modulating the Blood–Brain Barrier: A Comprehensive Review

Cited by 29 publications

References 259 publications

Inhibiting CK2 among Promising Therapeutic Strategies for Gliomas and Several Other Neoplasms

Inhibiting CK2 among Promising Therapeutic Strategies for Gliomas and Several Other Neoplasms

Polymeric Dendrimers as Nanocarrier Vectors for Neurotheranostics

Current Opportunities for Targeting Dysregulated Neurodevelopmental Signaling Pathways in Glioblastoma

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