Leva Momtazi1, Shahla Bagherifam2, Gurvinder Singh3, Antje Hofgaard4, Minna Hakkarainen5, Wilhelm R Glomm6, Norbert Roos7, Gunhild M Mælandsmo8, Gareth Griffiths9, Bo Nyström10. 1. Department of Chemistry, University of Oslo, P.O. Box 1033, Blindern, N-0315 Oslo, Norway. Electronic address: leva.momtazi@kjemi.uio.no. 2. Department of Chemistry, University of Oslo, P.O. Box 1033, Blindern, N-0315 Oslo, Norway; Department of Biology, University of Oslo, Blindernveien 31, 0316 Oslo, Norway. Electronic address: s.b.fam@kjemi.uio.no. 3. Department of Chemical Engineering, Norwegian University of Science and Technology, 7491 Trondheim, Norway. Electronic address: gurvinder.singh@ntnu.no. 4. Department of Biology, University of Oslo, Blindernveien 31, 0316 Oslo, Norway. Electronic address: antje.hofgaard@ibv.uio.no. 5. Department of Fiber and Polymer Technology, KTH Royal Institute of Technology, Teknikringen 56-58, 10044 Stockholm, Sweden. Electronic address: minna@kth.se. 6. Biotechnology and Nanomedicine Sector, SINTEF Materials and Chemistry, Sem Sælands vei 2A, N-7034 Trondheim, Norway. Electronic address: Wilhelm.Glomm@sintef.no. 7. Department of Biology, University of Oslo, Blindernveien 31, 0316 Oslo, Norway. Electronic address: norbert.roos@ibv.uio.no. 8. Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. Electronic address: Gunhild.Mari.Malandsmo@rr-research.no. 9. Department of Biology, University of Oslo, Blindernveien 31, 0316 Oslo, Norway. Electronic address: g.w.griffiths@ibv.uio.no. 10. Department of Chemistry, University of Oslo, P.O. Box 1033, Blindern, N-0315 Oslo, Norway. Electronic address: bo.nystrom@kjemi.uio.no.
Abstract
HYPOTHESIS: The absence of targetability is the primary inadequacy of conventional chemotherapy. Targeted drug delivery systems are conceptualized to overcome this challenge. We have designed a targetable magnetic nanocarrier consisting of a superparamagnetic iron oxide (SPIO) core and biocompatible and biodegradable poly(sebacic anhydride)-block-methyl ether poly(ethylene glycol) (PSA-mPEG) polymer shell. The idea is that this type of carriers should facilitate the targeting of cancer cells. EXPERIMENTS: PSA-mPEG was synthesized with poly-condensation and the in vitro degradation rate of the polymer was monitored by gel permeation chromatography (GPC). The magnetic nanocarriers were fabricated devoid of any surfactants and were capable of carrying high payload of hydrophobic dye. The successful encapsulation of SPIO within the polymer shell was confirmed by TEM. The results we obtained from measuring the size of SPIO loaded in polymeric NPs (SPIO-PNP) by dynamic light scattering (DLS) and iron content measurement of these particles by ICP-MS, indicate that SPIO is the most suitable carrier for cancer drug delivery applications. FINDINGS: Measuring the hydrodynamic radii of SPIO-PNPs by DLS over one month revealed the high stability of these particles at both body and room temperature. We further investigated the cell viability and cellular uptake of SPIO-PNPs in vitro with MDA-MB-231 breast cancer cells. We found that SPIO-PNPs induce negligible toxicity within a concentration range of 1-2μg/ml. The TEM micrographs of thin cross-sectioned MDA-MBA-231 cells showed internalization of SPIO-PNPs within size range of 150-200nm after 24h. This study has provided a foundation for eventually loading these nanoparticles with anti-cancer drugs for targeted cancer therapy using an external magnetic field.
HYPOTHESIS: The absence of targetability is the primary inadequacy of conventional chemotherapy. Targeted drug delivery systems are conceptualized to overcome this challenge. We have designed a targetable magnetic nanocarrier consisting of a superparamagnetic iron oxide (SPIO) core and biocompatible and biodegradable poly(sebacic anhydride)-block-methyl ether poly(ethylene glycol) (PSA-mPEG) polymer shell. The idea is that this type of carriers should facilitate the targeting of cancer cells. EXPERIMENTS: PSA-mPEG was synthesized with poly-condensation and the in vitro degradation rate of the polymer was monitored by gel permeation chromatography (GPC). The magnetic nanocarriers were fabricated devoid of any surfactants and were capable of carrying high payload of hydrophobic dye. The successful encapsulation of SPIO within the polymer shell was confirmed by TEM. The results we obtained from measuring the size of SPIO loaded in polymeric NPs (SPIO-PNP) by dynamic light scattering (DLS) and iron content measurement of these particles by ICP-MS, indicate that SPIO is the most suitable carrier for cancer drug delivery applications. FINDINGS: Measuring the hydrodynamic radii of SPIO-PNPs by DLS over one month revealed the high stability of these particles at both body and room temperature. We further investigated the cell viability and cellular uptake of SPIO-PNPs in vitro with MDA-MB-231 breast cancer cells. We found that SPIO-PNPs induce negligible toxicity within a concentration range of 1-2μg/ml. The TEM micrographs of thin cross-sectioned MDA-MBA-231 cells showed internalization of SPIO-PNPs within size range of 150-200nm after 24h. This study has provided a foundation for eventually loading these nanoparticles with anti-cancer drugs for targeted cancer therapy using an external magnetic field.