期刊
BIOMATERIALS
卷 52, 期 -, 页码 507-516出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2015.02.053
关键词
PAMAM dendrimer; Glioblastoma; Tumor penetration; Tumor associated macrophages; Biodistribution; Blood-brain barrier
资金
- NCI NIH HHS [P30 CA006973] Funding Source: Medline
Effective blood brain tumor barrier penetration and uniform solid tumor distribution can significantly enhance therapeutic delivery to brain tumors. Hydroxyl-functionalized, generation-4 poly(amidoamine) (PAMAM) dendrimers, with their small size, near-neutral surface charge, and the ability to selectively localize in cells associated with neuroinflammation may offer new opportunities to address these challenges. In this study we characterized the intracranial tumor biodistribution of systemically delivered PAMAM dendrimers in an intracranial rodent gliosarcoma model using fluorescence-based quantification methods and high resolution confocal microscopy. We observed selective and homogeneous distribution of dendrimer throughout the solid tumor (similar to 6 mm) and peritumoral area within fifteen minutes after systemic administration, with subsequent accumulation and retention in tumor associated microglia/macrophages (TAMs). Neuroinflammation and TAMs have important growth promoting and pro-invasive effects in brain tumors. The rapid clearance of systemically administered dendrimers from major organs promises minimal off-target adverse effects of conjugated drugs. Therefore, selective delivery of immunomodulatory molecules to TAM, using hydroxyl PAMAM dendrimers, may hold promise for therapy of glioblastoma. (c) 2015 Elsevier Ltd. All rights reserved.
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