{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T18:17:29Z","timestamp":1784657849549,"version":"3.55.0"},"reference-count":66,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T00:00:00Z","timestamp":1607904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Most available cancer chemotherapies are based on systemically administered small organic molecules, and only a tiny fraction of the drug reaches the disease site. The approach causes significant side effects and limits the outcome of the therapy. Targeted drug delivery provides an alternative to improve the situation. However, due to the poor release characteristics of the delivery systems, limitations remain. This report presents a new approach to address the challenges using two fundamentally different mechanisms to trigger the release from the liposomal carrier. We use an endogenous disease marker, an enzyme, combined with an externally applied magnetic field, to open the delivery system at the correct time only in the disease site. This site-activated release system is a novel two-switch nanomachine that can be regulated by a cell stress-induced enzyme at the cellular level and be remotely controlled using an applied magnetic field. We tested the concept using sphingomyelin-containing liposomes encapsulated with indocyanine green, fluorescent marker, or the anticancer drug cisplatin. We engineered the liposomes by adding paramagnetic beads to act as a receiver of outside magnetic energy. The developed multifunctional liposomes were characterized in vitro in leakage studies and cell internalization studies. The release system was further studied in vivo in imaging and therapy trials using a squamous cell carcinoma tumor in the mouse as a disease model. In vitro studies showed an increased release of loaded material when stress-related enzyme and magnetic field was applied to the carrier liposomes. The theranostic liposomes were found in tumors, and the improved therapeutic effect was shown in the survival studies.<\/jats:p>","DOI":"10.3390\/cancers12123767","type":"journal-article","created":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T22:30:52Z","timestamp":1607985052000},"page":"3767","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Lipid-Iron Nanoparticle with a Cell Stress Release Mechanism Combined with a Local Alternating Magnetic Field Enables Site-Activated Drug Release"],"prefix":"10.3390","volume":"12","author":[{"given":"Tuula","family":"Pe\u00f1ate Medina","sequence":"first","affiliation":[{"name":"Section Biomedical Imaging, Department of Radiology and Neuroradiology Universit\u00e4tsklinikum Schleswig-Holstein Campus Kiel, Christian Albrechts Universit\u00e4t zu Kiel, 24105 Kiel, Germany"},{"name":"Institute for Experimental Cancer Research, Christian-Albrechts-University Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirko","family":"Gerle","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Mund-, Kiefer- und Gesichtschirurgie, Universit\u00e4tsklinikum Schleswig-Holstein Campus Kiel, Christian Albrechts Universit\u00e4t zu Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8053-236X","authenticated-orcid":false,"given":"Jana","family":"Humbert","sequence":"additional","affiliation":[{"name":"Section Biomedical Imaging, Department of Radiology and Neuroradiology Universit\u00e4tsklinikum Schleswig-Holstein Campus Kiel, Christian Albrechts Universit\u00e4t zu Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanwen","family":"Chu","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Mund-, Kiefer- und Gesichtschirurgie, Universit\u00e4tsklinikum Schleswig-Holstein Campus Kiel, Christian Albrechts Universit\u00e4t zu Kiel, 24105 Kiel, Germany"},{"name":"Department of Oral and Maxillofacial Surgery, Second Affiliated Hospital, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Lena","family":"K\u00f6pnick","sequence":"additional","affiliation":[{"name":"Section Biomedical Imaging, Department of Radiology and Neuroradiology Universit\u00e4tsklinikum Schleswig-Holstein Campus Kiel, Christian Albrechts Universit\u00e4t zu Kiel, 24105 Kiel, Germany"},{"name":"Institute for Experimental Cancer Research, Christian-Albrechts-University Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Barkmann","sequence":"additional","affiliation":[{"name":"Section Biomedical Imaging, Department of Radiology and Neuroradiology Universit\u00e4tsklinikum Schleswig-Holstein Campus Kiel, Christian Albrechts Universit\u00e4t zu Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9315-4188","authenticated-orcid":false,"given":"Vasil M.","family":"Garamus","sequence":"additional","affiliation":[{"name":"Helmholtz-Zentrum Geesthacht, Zentrum f\u00fcr Material- und K\u00fcstenforschung GmbH, Max Planck Stra\u00dfe 1, 21502 Geesthacht, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Sanz","sequence":"additional","affiliation":[{"name":"Institute of Nanoscience of Aragon (INA) and Condensed Matter Physics Dept., University of Zaragoza, C.P. 50.018 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolai","family":"Purcz","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Mund-, Kiefer- und Gesichtschirurgie, Universit\u00e4tsklinikum Schleswig-Holstein Campus Kiel, Christian Albrechts Universit\u00e4t zu Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Will","sequence":"additional","affiliation":[{"name":"Section Biomedical Imaging, Department of Radiology and Neuroradiology Universit\u00e4tsklinikum Schleswig-Holstein Campus Kiel, Christian Albrechts Universit\u00e4t zu Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lia","family":"Appold","sequence":"additional","affiliation":[{"name":"Institute for Experimental Cancer Research, Christian-Albrechts-University Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5595-5205","authenticated-orcid":false,"given":"Timo","family":"Damm","sequence":"additional","affiliation":[{"name":"Section Biomedical Imaging, Department of Radiology and Neuroradiology Universit\u00e4tsklinikum Schleswig-Holstein Campus Kiel, Christian Albrechts Universit\u00e4t zu Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2361-5134","authenticated-orcid":false,"given":"Juho","family":"Suojanen","sequence":"additional","affiliation":[{"name":"Cleft Palate and Craniofacial Center, Department of Plastic Surgery, Helsinki University Hospital, 00029 HUS Helsinki, Finland"},{"name":"P\u00e4ij\u00e4t-H\u00e4me Joint Authority for Health and Wellbeing, Department of Oral and Maxillo-Facial Surgery, 15850 Lahti, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3273-9865","authenticated-orcid":false,"given":"Philipp","family":"Arnold","sequence":"additional","affiliation":[{"name":"Anatomical Institute, Christian-Albrechts-University Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph","family":"Lucius","sequence":"additional","affiliation":[{"name":"Anatomical Institute, Christian-Albrechts-University Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6004-6946","authenticated-orcid":false,"given":"Regina","family":"Willumeit-R\u00f6mer","sequence":"additional","affiliation":[{"name":"Helmholtz-Zentrum Geesthacht, Zentrum f\u00fcr Material- und K\u00fcstenforschung GmbH, Max Planck Stra\u00dfe 1, 21502 Geesthacht, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahya","family":"A\u00e7il","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Mund-, Kiefer- und Gesichtschirurgie, Universit\u00e4tsklinikum Schleswig-Holstein Campus Kiel, Christian Albrechts Universit\u00e4t zu Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg","family":"Wiltfang","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Mund-, Kiefer- und Gesichtschirurgie, Universit\u00e4tsklinikum Schleswig-Holstein Campus Kiel, Christian Albrechts Universit\u00e4t zu Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1558-9279","authenticated-orcid":false,"given":"Gerardo F.","family":"Goya","sequence":"additional","affiliation":[{"name":"Institute of Nanoscience of Aragon (INA) and Condensed Matter Physics Dept., University of Zaragoza, C.P. 50.018 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus C.","family":"Gl\u00fcer","sequence":"additional","affiliation":[{"name":"Section Biomedical Imaging, Department of Radiology and Neuroradiology Universit\u00e4tsklinikum Schleswig-Holstein Campus Kiel, Christian Albrechts Universit\u00e4t zu Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9878-5309","authenticated-orcid":false,"given":"Oula","family":"Pe\u00f1ate Medina","sequence":"additional","affiliation":[{"name":"Section Biomedical Imaging, Department of Radiology and Neuroradiology Universit\u00e4tsklinikum Schleswig-Holstein Campus Kiel, Christian Albrechts Universit\u00e4t zu Kiel, 24105 Kiel, Germany"},{"name":"Institute for Experimental Cancer Research, Christian-Albrechts-University Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,14]]},"reference":[{"key":"ref_1","first-page":"6387","article-title":"A new concept for macromolecular therapeutics in cancer chemotherapy: Mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs","volume":"46","author":"Matsumura","year":"1986","journal-title":"Cancer Res."},{"key":"ref_2","first-page":"541","article-title":"Phase II study of liposomal cisplatin (SPI-77) in platinum-sensitive recurrences of ovarian cancer","volume":"30","author":"Seetharamu","year":"2010","journal-title":"Anticancer. 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