TY - JOUR
T1 - A Heat-Activated Drug-Delivery Platform Based on Phosphatidyl-(oligo)-glycerol Nanocarrier for Effective Cancer Treatment
AU - Hossann, Martin
AU - Hirschberger, Johannes
AU - Schmidt, Rebecca
AU - Baumgartner, Christine
AU - Zimmermann, Katja
AU - Baer, Silke
AU - Ratzlaff, Christina
AU - Peller, Michael
AU - Troedson, Karin
AU - Limmer, Simone
AU - Brühschwein, Andreas
AU - Dörfelt, Rene
AU - Kreutzmann, Nina
AU - Wess, Gerhard
AU - Knösel, Thomas
AU - Schagon, Olaf
AU - Fischer, Johannes
AU - Grüll, Holger
AU - Willerding, Linus
AU - Schmidt, Michael
AU - Meyer-Lindenberg, Andrea
AU - Issels, Rolf D.
AU - Schwaiger, Markus
AU - Eggermont, Alexander M.
AU - ten Hagen, Timo L.
AU - Lindner, Lars H.
N1 - Publisher Copyright:
© 2021 The Authors. Advanced NanoBiomed Research published by Wiley-VCH GmbH.
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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.
KW - drug delivery
KW - hyperthermia
KW - nanomedicines
KW - neoadjuvants
KW - phosphatidyloligoglycerol
KW - soft tissue sarcoma
KW - thermosensitive liposomes
UR - http://www.scopus.com/inward/record.url?scp=85165515437&partnerID=8YFLogxK
U2 - 10.1002/anbr.202000089
DO - 10.1002/anbr.202000089
M3 - Article
AN - SCOPUS:85165515437
SN - 2699-9307
VL - 1
JO - Advanced NanoBiomed Research
JF - Advanced NanoBiomed Research
IS - 6
M1 - 2000089
ER -
