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

JOURNAL OF CONTROLLED RELEASE

卷:294

Article

Ullah, Sami¹  Seidel, Katja^2,3  Tuerkkan, Sibel^2,3  Warwas, Dawid Peter⁴  Dubich, Tatyana¹  Rohde, Manfred⁵  Hauser, Hansjoerg⁶  Behrens, Peter⁴  Kirschning, Andreas^2,3  Koester, Mario¹  Wirth, Dagmar^1,7 

[1] Helmholtz Ctr Infect Res, Model Syst Infect & Immun, Inhoffenstr 7, D-38124 Braunschweig, Germany

[2] Leibniz Univ Hannover, Inst Organ Chem, Hannover, Germany

[3] Leibniz Univ Hannover, Ctr Biomol Drug Res BMWZ, Hannover, Germany

[4] Leibniz Univ Hannover, Inst Inorgan Chem, Hannover, Germany

[5] Helmholtz Ctr Infect Res, Cent Facil Microscopy, Braunschweig, Germany

[6] Helmholtz Ctr Infect Res, Sci Strategy, Braunschweig, Germany

[7] Hannover Med Sch, Inst Expt Hematol, Hannover, Germany

关键词: Cell based drug delivery;    Macrophages;    Magnetic silica nanoparticles;    Hyperthermia;    Controlled drug delivery;    3D tumour model;   

DOI  :  10.1016/j.jconrel.2018.12.040

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free