期刊
JOURNAL OF CONTROLLED RELEASE
卷 294, 期 -, 页码 327-336出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2018.12.040
关键词
Cell based drug delivery; Macrophages; Magnetic silica nanoparticles; Hyperthermia; Controlled drug delivery; 3D tumour model
资金
- Deutsche Forschungsgemeinschaft, Germany (DFG) [WI2648/3-1, BE1664/21-1]
- Cluster of Excellence REBIRTH (From Regenerative Biology to Reconstructive Therapy)
- ministry of Lower Saxony, Germany
- Volkswagen Stiftung, Germany [VWZN2860]
- Ministry of Science and Culture of Lower Saxony, Germany
- DAAD, Germany
- HZI graduate school
Targeted delivery of drugs is a major challenge in treatment of diverse diseases. Systemically administered drugs demand high doses and are accompanied by poor selectivity and side effects on non-target cells. Here, we introduce a new principle for targeted drug delivery. It is based on macrophages as transporters for nanoparticle-coupled drugs as well as controlled release of drugs by hyperthermia mediated disruption of the cargo cells and simultaneous deliberation of nanoparticle-linked drugs. Hyperthermia is induced by an alternating electromagnetic field (AMF) that induces heat from silica-coated superparamagnetic iron oxide nanoparticles (SPIONs). We show proof-of-principle of controlled release by the simultaneous disruption of the cargo cells and the controlled, AMF induced release of a toxin, which was covalently linked to silica-coated SPIONs via a thermo-sensitive linker. Cells that had not been loaded with SPIONs remain unaffected. Moreover, in a 3D co-culture model we demonstrate specific killing of associated tumour cells when employing a ratio as low as 1:40 (SPION-loaded macrophage: tumour cells). Overall, our results demonstrate that AMF induced drug release from macrophage-entrapped nanoparticles is tightly controlled and may be an attractive novel strategy for targeted drug release.
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