期刊
BIOMATERIALS
卷 35, 期 9, 页码 2859-2867出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.12.001
关键词
Cancer initiating cells; Glioblastoma; Controlled release; Bone morphogenetic protein; Microspheres; PLGA
资金
- Ministerio de Ciencia e Innovacion
- Programa de Investigacion en Salud [PS09/1786]
- Xunta de Galicia [EM2013/042]
- Agencia Espanola de Cooperacion Internacional
- Asociacion Espanola contra el Cancer
- Xunta de Galicia
Designing therapeutic devices capable of manipulating glioblastoma initiating cells (GICs) is critical to stop tumor recurrence and its associated mortality. Previous studies have indicated that bone morphogenetic protein-7 (BMP-7) acts as an endogenous suppressor of GICs, and thus, it could become a treatment for this cancer. In this work, we engineer an implantable microsphere system optimized for the controlled release of BMP-7 as a bioinspired therapeutic device against GICs. This microsphere delivery system is based on the formation of a heparin-BMP-7 nanocomplex, first coated with Tetronic (R) and further entrapped in a biodegradable polyester matrix. The obtained microspheres can efficiently encapsulate BMP-7, and release it in a controlled manner with minimum burst effect for over two months while maintaining protein bioactivity. Released BMP-7 showed a remarkable capacity to stop tumor formation in a GICs cell culture model, an effect that could be mediated by forced reprogramming of tumorigenic cells towards a non-tumorigenic astroglial lineage. (C) 2013 Elsevier Ltd. All rights reserved.
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