Brain Cancer Chemotherapy through a Delivery System across the Blood-Brain Barrier into the Brain Based on Receptor-Mediated Transcytosis Using Monoclonal Antibody Conjugates

Tashima, Toshihiko

doi:10.3390/biomedicines10071597

Cited by 14 publications

(8 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Research has highlighted the potential to use these receptor-mediated transcytosis (RMT) of ADCs for non-invasive drug delivery [ 11 , 32 ]. RMT entails several steps that are initiated by ligand-receptor binding and endocytosis and then guided by intracellular trafficking and vesicle fusion to arrive at the targeted location [ 32 , 40 ]. In clinical trials, the most common targets including transferrin receptor, insulin receptor, and members of low-density lipoprotein receptor related proteins (LRP).…”

Section: Therapeutic Strategies In Bbb Opening and Deliverymentioning

confidence: 99%

Translational strategies and systems biology insights for blood-brain barrier opening and delivery in brain tumors and Alzheimer’s disease

Song,

Plumlee,

Ahn

et al. 2023

Biomedicine & Pharmacotherapy

View full text Add to dashboard Cite

Section: Therapeutic Strategies In Bbb Opening and Deliverymentioning

confidence: 99%

Translational strategies and systems biology insights for blood-brain barrier opening and delivery in brain tumors and Alzheimer’s disease

Song,

Plumlee,

Ahn

et al. 2023

Biomedicine & Pharmacotherapy

View full text Add to dashboard Cite

“…(b) Main intake transport routes of the BBB. Adapted with permission from (Naqvi et al, 2020; Sorets et al, 2020; Tashima, 2022). (c) Physiological differences between the GBM BBB (tumor invasive margins) and BBTB (tumor core).…”

Section: Gbm Niches Key Cell Players and Tmementioning

confidence: 99%

Multi‐ligand functionalized blood‐to‐tumor sequential targeting strategies in the field of glioblastoma nanomedicine

Martins

Sarmento

2023

WIREs Nanomed Nanobiotechnol

View full text Add to dashboard Cite

Glioblastoma (GBM) is an unmet clinical need characterized by a standard of care (SOC) 5‐year survival rate of only 5%, and a treatment mostly palliative. Significant hurdles in GBM therapies include an effective penetration of therapeutics through the brain protective barrier, namely the blood–brain barrier (BBB), and a successful therapeutic delivery to brain‐invading tumor cells post‐BBB crossing. These hurdles, along with the poor prognosis and critical heterogeneity of the disease, have shifted attention to treatment modalities with capacity to precisely and sequentially target (i) BBB cells, inducing blood‐to‐brain transport, and (ii) GBM cells, leading to a higher therapeutic accumulation at the tumor site. This sequential targeting allows therapeutic molecules to reach the brain parenchyma and compromise molecular processes that support tumor cell invasion. Besides improving formulation and pharmacokinetics constraints of drugs, nanomedicines offer the possibility of being surface functionalized with multiple possibilities of targeting ligands, while delivering the desired therapeutic cargos to the biological sites of interest. Targeting ligands exploit the site‐specific expression or overexpression of specific molecules on BBB and GBM cells, triggering brain plus tumor transport. Since the efficacy of single‐ligand functionalized nanomedicines is limited due to the GBM anatomical site (brain) and disease complexity, this review presents an overview of multi‐ligand functionalized, BBB and GBM sequentially‐ and dual‐targeted nanomedicines reported in literature over the last 10 years. The role of the BBB in GBM progression, treatment options, and the multiple possibilities of currently available targeting ligands will be summarized.This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

show abstract

“…The specificity of targeting in relation to the delivery of such drugs would depend on the presence of an increased number of transferrin receptors, which are mainly present on selected cancer cell types. The use of antibodies and other interventions against transferrin receptors is another rapidly growing area of anticancer targeting [221][222][223].…”

Section: Protein Interactions Of Chelators and Chelator-iron Complexe...mentioning

confidence: 99%

New Iron Metabolic Pathways and Chelation Targeting Strategies Affecting the Treatment of All Types and Stages of Cancer

Kontoghiorghes¹

2022

IJMS

View full text Add to dashboard Cite

There is new and increasing evidence from in vitro, in vivo and clinical studies implicating the pivotal role of iron and associated metabolic pathways in the initiation, progression and development of cancer and in cancer metastasis. New metabolic and toxicity mechanisms and pathways, as well as genomic, transcription and other factors, have been linked to cancer and many are related to iron. Accordingly, a number of new targets for iron chelators have been identified and characterized in new anticancer strategies, in addition to the classical restriction of/reduction in iron supply, the inhibition of transferrin iron delivery, the inhibition of ribonucleotide reductase in DNA synthesis and high antioxidant potential. The new targets include the removal of excess iron from iron-laden macrophages, which affects anticancer activity; the modulation of ferroptosis; ferritin iron removal and the control of hyperferritinemia; the inhibition of hypoxia related to the role of hypoxia-inducible factor (HIF); modulation of the function of new molecular species such as STEAP4 metalloreductase and the metastasis suppressor N-MYC downstream-regulated gene-1 (NDRG1); modulation of the metabolic pathways of oxidative stress damage affecting mitochondrial function, etc. Many of these new, but also previously known associated iron metabolic pathways appear to affect all stages of cancer, as well as metastasis and drug resistance. Iron-chelating drugs and especially deferiprone (L1), has been shown in many recent studies to fulfill the role of multi-target anticancer drug linked to the above and also other iron targets, and has been proposed for phase II trials in cancer patients. In contrast, lipophilic chelators and their iron complexes are proposed for the induction of ferroptosis in some refractory or recurring tumors in drug resistance and metastasis where effective treatments are absent. There is a need to readdress cancer therapy and include therapeutic strategies targeting multifactorial processes, including the application of multi-targeting drugs involving iron chelators and iron–chelator complexes. New therapeutic protocols including drug combinations with L1 and other chelating drugs could increase anticancer activity, decrease drug resistance and metastasis, improve treatments, reduce toxicity and increase overall survival in cancer patients.

show abstract

Brain Cancer Chemotherapy through a Delivery System across the Blood-Brain Barrier into the Brain Based on Receptor-Mediated Transcytosis Using Monoclonal Antibody Conjugates

Cited by 14 publications

References 55 publications

Translational strategies and systems biology insights for blood-brain barrier opening and delivery in brain tumors and Alzheimer’s disease

Translational strategies and systems biology insights for blood-brain barrier opening and delivery in brain tumors and Alzheimer’s disease

Multi‐ligand functionalized blood‐to‐tumor sequential targeting strategies in the field of glioblastoma nanomedicine

New Iron Metabolic Pathways and Chelation Targeting Strategies Affecting the Treatment of All Types and Stages of Cancer

Contact Info

Product

Resources

About