Preclinical effects of CRLX101, an investigational camptothecin-containing nanoparticle drug conjugate, on treating glioblastoma multiforme via apoptosis and antiangiogenesis

Chien Ju Lin, Yi Ling Lin, Frank Luh, Yun Yen, Ruei Ming Chen

研究成果: 雜誌貢獻文章

14 引文 (Scopus)

摘要

Malignant gliomas are difficult to treat in clinical practice. This study was aimed to investigate the preclinical efficacy of CRLX101, an investigational nanoparticle-drug conjugate developed by conjugating camptothecin (CPT) with cyclodextrin-polyethylene glycol, against gliomas. CPT fluorescence was detected across tight-junction barriers and in mouse plasma and brain. Following CRLX101 treatment, CPT was distributed in the cytoplasm of human U87 MG glioma cells. U87 MG cell viability was decreased by CRLX101 and CPT. Moreover, CRLX101 induced less cytotoxicity to human astrocytes compared to CPT. Exposure of U87 MG cells to CRLX101 induced G2/M cell cycle arrest and apoptosis. Administration of CRLX101 induced apoptosis in mice brain tumor tissues and prolonged the survival rate of mice. In addition, CRLX101 inhibited hypoxia and angiogenesis by suppressing the expression of carbonic anhydrase IX, vascular endothelial growth factor, and CD31 in tumor sections. Taken together, this preclinical study showed that CRLX101 possesses antitumor abilities by inducing cell cycle arrest and apoptosis in glioma cells and inhibiting tumor angiogenesis, thereby prolonging the lifespan of mice bearing intracranial gliomas. These data support further research of CRLX101 in patients with brain tumors.
原文英語
頁(從 - 到)42408-42421
頁數14
期刊Oncotarget
7
發行號27
DOIs
出版狀態已發佈 - 七月 5 2016

指紋

Camptothecin
Glioblastoma
Nanoparticles
Apoptosis
Glioma
Pharmaceutical Preparations
Brain Neoplasms
G2 Phase Cell Cycle Checkpoints
Investigational Drugs
IT-101
Tissue Survival
Tight Junctions
Cyclodextrins
Cell Cycle Checkpoints
Astrocytes
Vascular Endothelial Growth Factor A
Neoplasms
Cell Survival
Cytoplasm
Survival Rate

ASJC Scopus subject areas

  • Oncology

引用此文

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abstract = "Malignant gliomas are difficult to treat in clinical practice. This study was aimed to investigate the preclinical efficacy of CRLX101, an investigational nanoparticle-drug conjugate developed by conjugating camptothecin (CPT) with cyclodextrin-polyethylene glycol, against gliomas. CPT fluorescence was detected across tight-junction barriers and in mouse plasma and brain. Following CRLX101 treatment, CPT was distributed in the cytoplasm of human U87 MG glioma cells. U87 MG cell viability was decreased by CRLX101 and CPT. Moreover, CRLX101 induced less cytotoxicity to human astrocytes compared to CPT. Exposure of U87 MG cells to CRLX101 induced G2/M cell cycle arrest and apoptosis. Administration of CRLX101 induced apoptosis in mice brain tumor tissues and prolonged the survival rate of mice. In addition, CRLX101 inhibited hypoxia and angiogenesis by suppressing the expression of carbonic anhydrase IX, vascular endothelial growth factor, and CD31 in tumor sections. Taken together, this preclinical study showed that CRLX101 possesses antitumor abilities by inducing cell cycle arrest and apoptosis in glioma cells and inhibiting tumor angiogenesis, thereby prolonging the lifespan of mice bearing intracranial gliomas. These data support further research of CRLX101 in patients with brain tumors.",
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AU - Luh, Frank

AU - Yen, Yun

AU - Chen, Ruei Ming

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AB - Malignant gliomas are difficult to treat in clinical practice. This study was aimed to investigate the preclinical efficacy of CRLX101, an investigational nanoparticle-drug conjugate developed by conjugating camptothecin (CPT) with cyclodextrin-polyethylene glycol, against gliomas. CPT fluorescence was detected across tight-junction barriers and in mouse plasma and brain. Following CRLX101 treatment, CPT was distributed in the cytoplasm of human U87 MG glioma cells. U87 MG cell viability was decreased by CRLX101 and CPT. Moreover, CRLX101 induced less cytotoxicity to human astrocytes compared to CPT. Exposure of U87 MG cells to CRLX101 induced G2/M cell cycle arrest and apoptosis. Administration of CRLX101 induced apoptosis in mice brain tumor tissues and prolonged the survival rate of mice. In addition, CRLX101 inhibited hypoxia and angiogenesis by suppressing the expression of carbonic anhydrase IX, vascular endothelial growth factor, and CD31 in tumor sections. Taken together, this preclinical study showed that CRLX101 possesses antitumor abilities by inducing cell cycle arrest and apoptosis in glioma cells and inhibiting tumor angiogenesis, thereby prolonging the lifespan of mice bearing intracranial gliomas. These data support further research of CRLX101 in patients with brain tumors.

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