Journal article
Alpha Particle Enhanced Blood Brain/Tumor Barrier Permeabilization in Glioblastomas Using Integrin Alpha-v Beta-3-Targeted Liposomes
Molecular cancer therapeutics, Vol.16(10), pp.2191-2200
10/01/2017
DOI: 10.1158/1535-7163.MCT-16-0907
PMCID: PMC5628117
PMID: 28619756
Abstract
Glioblastoma (GBM) is the most common primary malignant astrocytoma characterized by extensive invasion, angiogenesis, hypoxia, and micrometastasis. Despite the relatively leaky nature of GBM blood vessels, effective delivery of antitumor therapeutics has been a major challenge due to the complications caused by the blood-brain barrier (BBB) and the highly torturous nature of newly formed tumor vasculature (blood tumor barrier-BTB). External beam radiotherapy was previously shown to be an effective means of permeabilizing central nervous system (CNS) barriers. By using targeted short-ranged radionuclides, we show for the first time that our targeted actinium-225-labeled alpha(v)beta(3)-specific liposomes (Ac-225-IA-TLs) caused catastrophic double stranded DNA breaks and significantly enhanced the permeability of BBB and BTB in mice bearing orthotopic GBMs. Histologic studies revealed characteristic a-particle induced double strand breaks within tumors but was not significantly present in normal brain regions away from the tumor where BBB permeability was observed. These findings indicate that the enhanced vascular permeability in these distal regions did not result from direct a-particle-induced DNA damage. On the basis of these results, in addition to their direct antitumor effects, Ac-225-IA-TLs can potentially be used to enhance the permeability of BBB and BTB for effective delivery of systemically administered antitumor therapeutics. (C) 2017 AACR.
Details
- Title: Subtitle
- Alpha Particle Enhanced Blood Brain/Tumor Barrier Permeabilization in Glioblastomas Using Integrin Alpha-v Beta-3-Targeted Liposomes
- Creators
- Anirudh Sattiraju - Wake Forest UniversityXiaobing Xiong - Wake Forest Sch Med, Dept Radiol, Winston Salem, NC USADarpan N. Pandya - Wake Forest UniversityThaddeus J. Wadas - Wake Forest UniversityAng Xuan - Zhengzhou UniversityYao Sun - Wake Forest UniversityYoungkyoo Jung - Wake Forest UniversityKiran Kumar Solingapuram Sai - Wake Forest UniversityJay F. Dorsey - University of PennsylvaniaKing C. Li - Wake Forest UniversityAkiva Mintz - Columbia University
- Resource Type
- Journal article
- Publication Details
- Molecular cancer therapeutics, Vol.16(10), pp.2191-2200
- DOI
- 10.1158/1535-7163.MCT-16-0907
- PMID
- 28619756
- PMCID
- PMC5628117
- NLM abbreviation
- Mol Cancer Ther
- ISSN
- 1535-7163
- eISSN
- 1538-8514
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 10
- Grant note
- R21NS067471 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) 124443-MRSG-13-121-01-CDD / American Cancer Society R01CA181429 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) 1R01CA179072 01A1; R01 CA184091 01; P30 CA012197 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 10/01/2017
- Academic Unit
- Radiology; Radiation Oncology
- Record Identifier
- 9984312971102771
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