Macrophage entrapped silica coated superparamagnetic iron oxide particles for controlled drug release in a 3D cancer model

• Published in: Journal of controlled release 2019-01, Vol.294, p.327-336
• Main Authors: Ullah, Sami, Seidel, Katja, Türkkan, Sibel, Warwas, Dawid Peter, Dubich, Tatyana, Rohde, Manfred, Hauser, Hansjörg, Behrens, Peter, Kirschning, Andreas, Köster, Mario, Wirth, Dagmar
• Format: Article
• Language: English
• Subjects: Animals; Cell based drug delivery; Cell Line; Coculture Techniques; Controlled drug delivery, 3D tumour model; Delayed-Action Preparations - administration & dosage; Drug Delivery Systems; Drug Liberation; Ferric Compounds - administration & dosage; Ferric Compounds - chemistry; Humans; Hyperthermia; Hyperthermia, Induced; Macrophages; Magnetic Phenomena; Magnetic silica nanoparticles; Maytansine - administration & dosage; Mice; Models, Biological; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Neoplasms - drug therapy; Silicon Dioxide - administration & dosage; Silicon Dioxide - chemistry
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2018.12.040

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. [Display omitted]