Nanoparticles Surmounting Blood–Brain Tumor Barrier Through Both Transcellular and Paracellular Pathways to Target Brain Metastases

2019 ◽  
pp. 1900259 ◽  
Author(s):  
Tongtong Miao ◽  
Xiufeng Ju ◽  
Qiuning Zhu ◽  
Yamei Wang ◽  
Qian Guo ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Brain Metastases ◽  
Blood Brain ◽  
Paracellular Pathways

scholarly journals Lipid polymeric nanoparticles modified with tight junction-modulating peptides promote afatinib delivery across a blood–brain barrier model

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yu-Li Lo ◽  
Hua-Ching Lin ◽  
Shu-Ting Hong ◽  
Chih-Hsien Chang ◽  
Chen-Shen Wang ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Tight Junction ◽  
Blood Brain Barrier ◽  
Polymeric Nanoparticles ◽  
Growth Factor Receptor ◽  
Brain Barrier ◽  
Polymeric Nanoparticle ◽  
Blood Brain ◽  
Blood Brain Barrier Model ◽  
Delivery Platform

Abstract Background Brain metastases from non-small cell lung cancer (NSCLC) remain one of the most challenging malignancies. Afatinib (Afa) is an orally administered irreversible ErbB family blocker approved for epidermal growth factor receptor (EGFR)-mutated NSCLC. However, the incidence of brain metastases in patients with NSCLC and EGFR mutation is high. One of the major obstacles in the treatment of brain metastases is to transport drugs across the blood–brain barrier (BBB). A lipid polymeric nanoparticle (LPN) modified with a tight junction-modulating peptide is a potential formulation to deliver therapeutics across the BBB. FD7 and CCD are short peptides that perturb the tight junctions (TJs) of the BBB. In this study, the use of LPN modified with FD7 or CCD as a delivery platform was explored to enhance Afa delivery across the BBB model of mouse brain-derived endothelial bEnd.3 cells. Results Our findings revealed that Afa/LPN-FD7 and Afa/LPN-CCD exhibited a homogeneous shape, a uniform nano-scaled particle size, and a sustained-release profile. FD7, CCD, Afa/LPN-FD7, and Afa/LPN-CCD did not cause a significant cytotoxic effect on bEnd.3 cells. Afa/LPN-FD7 and Afa/LPN-CCD across the bEnd.3 cells enhanced the cytotoxicity of Afa on human lung adenocarcinoma PC9 cells. FD7 and CCD-modulated TJ proteins, such as claudin 5 and ZO-1, reduced transendothelial electrical resistance, and increased the permeability of paracellular markers across the bEnd.3 cells. Afa/LPN-FD7 and Afa/LPN-CCD were also partially transported through clathrin- and caveolae-mediated transcytosis, revealing the effective activation of paracellular and transcellular pathways to facilitate Afa delivery across the BBB and cytotoxicity of Afa on PC9 cells. Conclusion TJ-modulating peptide-modified LPN could be a prospective platform for the delivery of chemotherapeutics across the BBB to the brain for the potential treatment of the BM of NSCLC.

scholarly journals MET-04 A case of Brain Metastases with repeated bleeding from Esophageal carcinoma

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii19-ii19
Author(s):  
Masataka Mikai ◽  
Mitsuyoshi Abe ◽  
Yo watanabe ◽  
Chie Nakada ◽  
Yutaka Huchinoue ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Brain Metastases ◽  
Esophageal Carcinoma ◽  
Cell Carcinoma ◽  
Small Cell Carcinoma ◽  
Cerebral Hemorrhage ◽  
Small Cell ◽  
The Body ◽  
Metastatic Brain Tumor ◽  
Carcinoma Of The Esophagus

Abstract Brain metastases from esophageal cancer is rare and the incidence has been reported at approximately 5%. We report a case of brain metastases with repeated bleeding from Esophageal carcinoma. The case is a 76-year-old man. Three years ago he was diagnosed with small cell carcinoma of the esophagus by endoscopic biopsy. Metastasis was found only in the cervical lymph node, but the condition was stable by chemoradiotherapy and no metastases were found throughout the body before 1 month. He was admitted to the hospital because of a sudden convulsion, and CT scan revealed cerebral hemorrhage in the right frontal lobe. We performed conservative treatment, but rebleeding was observed from the same site repeatedly after 1 month and 2 months. Due to the influence of bleeding, it was difficult to distinguish cerebral hemorrhage from brain tumor by contrast MRI. After surgery, the cause of bleeding was diagnosed as metastatic brain tumor of esophageal small cell carcinoma. Postoperative radiation therapy was performed in another hospital, but rebleeding was observed 3 months after the operation. A reoperation was performed at another hospital, and a recurrence of metastatic brain tumor was diagnosed. In the case of highly malignant metastatic brain tumors, it was considered necessary to frequently follow the images.

scholarly journals Molecular Mechanisms of Drug Resistance in Glioblastoma

2021 ◽  
Vol 22 (12) ◽  
pp. 6385
Author(s):  
Maya A. Dymova ◽  
Elena V. Kuligina ◽  
Vladimir A. Richter
Keyword(s):  
Drug Resistance ◽  
Brain Tumor ◽  
Molecular Mechanisms ◽  
Primary Brain Tumor ◽  
Therapeutic Resistance ◽  
Molecular Characteristics ◽  
Blood Brain ◽  
Conventional Radiation ◽  
The Brain ◽  
Made In

Glioblastoma multiforme (GBM) is the most common and fatal primary brain tumor, is highly resistant to conventional radiation and chemotherapy, and is not amenable to effective surgical resection. The present review summarizes recent advances in our understanding of the molecular mechanisms of therapeutic resistance of GBM to already known drugs, the molecular characteristics of glioblastoma cells, and the barriers in the brain that underlie drug resistance. We also discuss the progress that has been made in the development of new targeted drugs for glioblastoma, as well as advances in drug delivery across the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB).

scholarly journals TMIC-34. IN VITRO STUDY OF ROLE OF ASTROCYTIC S1P3 IN REGULATING BLOOD-BRAIN/TUMOR BARRIER PERMEABILITY

2017 ◽  
Vol 19 (suppl_6) ◽  
pp. vi250-vi250
Author(s):  
Anurag N Paranjape ◽  
Brunilde Gril ◽  
Stephan Woditschka ◽  
Jeffrey Hanson ◽  
Xiaolin Wu ◽  
...  
Keyword(s):  
Brain Tumor ◽  
In Vitro Study ◽  
Vitro Study ◽  
Barrier Permeability ◽  
Blood Brain
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