A Heat‐Activated Drug‐Delivery Platform Based on Phosphatidyl‐(oligo)‐glycerol Nanocarrier for Effective Cancer Treatment

Advanced NanoBiomed Research

Karin Troedson¹  Gerhard Wess¹  Christina Ratzlaff¹  Rene Dörfelt¹  Nina Kreutzmann¹  Silke Baer¹  Johannes Hirschberger¹  Katja Zimmermann¹  Andrea Meyer-Lindenberg²  Andreas Brühschwein²  Rolf D. Issels³  Lars H. Lindner³  Martin Hossann³  Linus Willerding³  Rebecca Schmidt³  Simone Limmer³  Markus Schwaiger⁴  Christine Baumgartner⁴  Johannes Fischer⁴  Timo L. ten Hagen⁵  Michael Peller⁶  Thomas Knösel⁷  Michael Schmidt⁸  Olaf Schagon⁹  Alexander M. Eggermont^1,10  Holger Grüll^1,11 

[1] Clinic of Small Animal Medicine LMU Munich Veterinärstr. 13 80539 Munich Germany;Clinic of Small Animal Surgery and Reproduction LMU Munich Veterinärstr. 13 80539 Munich Germany;Department of Medicine III & Sarcoma Center (SarKUM) University Hospital LMU Munich Marchioninistraße 15 81377 Munich Germany;Department of Nuclear Medicine Klinikum Rechts der Isar Ismaninger Straße 22 81675 Munich Germany;Department of Pathology Laboratory Experimental Oncology and Nanomedicine Innovation Center Erasmus (NICE) Erasmus MC 3015 CE Rotterdam The Netherlands;Department of Radiology University Hospital LMU Munich Marchioninistr. 15 81377 Munich Germany;Institute of Pathology LMU Munich Thalkirchner Str. 36 80337 Munich Germany;Munich Cancer Registry Institute for Medical Information Processing, Biometry, and Epidemiology University of Munich Marchioninistr. 15 81377 Munich Germany;Phospholipid Research Group Max Planck Institute for Biophysical Chemistry Am Faßberg 11 37073 Göttingen Germany;Princess Máxima Center for Pediatric Oncology University Medical Center Utrecht Heidelberglaan 25 3584 CS Utrecht The Netherlands;University of Cologne Faculty of Medicine University Hospital of Cologne Institute of Diagnostic and Interventional Radiology Kerpener Str. 62 50937 Cologne Germany;

关键词: drug delivery;    hyperthermia;    nanomedicines;    neoadjuvants;    phosphatidyloligoglycerol;    soft tissue sarcoma;   

DOI  :  10.1002/anbr.202000089

来源: DOAJ

【 摘 要 】

The potential of cancer drugs is not fully exploited due to low tumor uptake and occurrence of systemic side effects, limiting maximum tolerated dose. Actively targeted nanocarriers improve efficacy while minimizing off‐target toxicity. Herein, it is the first time a drug‐delivery platform for heat‐triggered intravascular drug release is described, based on synthetic phosphatidyl‐(oligo)‐glycerols from organic synthesis to preclinical investigation in feline patients. For the nanocarrier formulated doxorubicin (DOX), superior tumor drug delivery and antitumor activity compared with free DOX, conventional liposomal DOX (Caelyx), and temperature‐sensitive lysolipid‐containing DOX‐liposomes in rat sarcoma are demonstrated. In a comparative oncological study with neoadjuvant treatment of feline sarcoma, a metabolic response determined with 18 F‐FDG‐positron emission tomography/magnetic resonance imaging (PET/MRI) and histopathological response after tumor resection are significantly better compared with free DOX, potentially by overcoming drug resistance based on improved intratumoral drug distribution. This novel drug‐delivery platform has great potential for the treatment of locally advanced tumors in humans.

【 授权许可】

Unknown