TY - JOUR

T1 - Macrophage entrapped silica coated superparamagnetic iron oxide particles for controlled drug release in a 3D cancer model

AU - Ullah, Sami

AU - Seidel, Katja

AU - Türkkan, Sibel

AU - Warwas, Dawid Peter

AU - Dubich, Tatyana

AU - Rohde, Manfred

AU - Hauser, Hansjörg

AU - Behrens, Peter

AU - Kirschning, Andreas

AU - Köster, Mario

AU - Wirth, Dagmar

N1 - Funding information: This work was supported by grants from Deutsche Forschungsgemeinschaft, Germany (DFG, WI2648/3-1 , BE1664/21-1 ), the Cluster of Excellence REBIRTH (From Regenerative Biology to Reconstructive Therapy) as well as from the Biofabrication for NIFE initiative, which is financially supported by the ministry of Lower Saxony, Germany, and the Volkswagen Stiftung, Germany (BIOFABRICATION FOR NIFE: VWZN2860 ). Further support came from the Ministry of Science and Culture of Lower Saxony, Germany, (MWK; graduate program Hannover School of Nanotechnology hosted by the Laboratory of Nano and Quantum Engineering (LNQE), Leibniz University Hannover ). S.U. wishes to acknowledge the HZI graduate school and DAAD, Germany, for support. S. T. was also supported by the DAAD, Germany . We thank I. Schleicher for assistance in the electron microscopy studies. Further thanks go to the LNQE for the use of their TEM equipment. This work was supported by grants from Deutsche Forschungsgemeinschaft, Germany (DFG, WI2648/3-1, BE1664/21-1), the Cluster of Excellence REBIRTH (From Regenerative Biology to Reconstructive Therapy) as well as from the Biofabrication for NIFE initiative, which is financially supported by the ministry of Lower Saxony, Germany, and the Volkswagen Stiftung, Germany (BIOFABRICATION FOR NIFE: VWZN2860). Further support came from the Ministry of Science and Culture of Lower Saxony, Germany, (MWK; graduate program Hannover School of Nanotechnology hosted by the Laboratory of Nano and Quantum Engineering (LNQE), Leibniz University Hannover). S.U. wishes to acknowledge the HZI graduate school and DAAD, Germany, for support. S. T. was also supported by the DAAD, Germany. We thank I. Schleicher for assistance in the electron microscopy studies. Further thanks go to the LNQE for the use of their TEM equipment.

PY - 2019/1/28

Y1 - 2019/1/28

N2 - 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.

AB - 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.

KW - Cell based drug delivery

KW - Controlled drug delivery, 3D tumour model

KW - Hyperthermia

KW - Macrophages

KW - Magnetic silica nanoparticles

KW - Cell Line

KW - Nanoparticles/administration & dosage

KW - Silicon Dioxide/administration & dosage

KW - Coculture Techniques

KW - Ferric Compounds/administration & dosage

KW - Humans

KW - Neoplasms/drug therapy

KW - Drug Delivery Systems

KW - Maytansine/administration & dosage

KW - Animals

KW - Magnetic Phenomena

KW - Models, Biological

KW - Hyperthermia, Induced

KW - Drug Liberation

KW - Mice

KW - Delayed-Action Preparations/administration & dosage

UR - http://www.scopus.com/inward/record.url?scp=85059177725&partnerID=8YFLogxK

U2 - 10.1016/j.jconrel.2018.12.040

DO - 10.1016/j.jconrel.2018.12.040

M3 - Article

C2 - 30586597

AN - SCOPUS:85059177725

VL - 294

SP - 327

EP - 336

JO - Journal of controlled release

JF - Journal of controlled release

SN - 0168-3659

ER -