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High‐Load Gemcitabine Inorganic–Organic Hybrid Nanoparticles as an Image‐Guided Tumor‐Selective Drug‐Delivery System to Treat Pancreatic Cancer

Ischyropoulou, Myrto; Sabljo, Kristina 1; Schneider, Leonie 2; Niemeyer, Christof M. ORCID iD icon 2; Napp, Joanna; Feldmann, Claus 1; Alves, Frauke
1 Institut für Anorganische Chemie (AOC), Karlsruher Institut für Technologie (KIT)
2 Institut für Biologische Grenzflächen (IBG), Karlsruher Institut für Technologie (KIT)

Abstract:

Pancreatic ductal adenocarcinoma (PDAC) has a devastating prognosis without effective treatment options. Thus, there is an urgent need for more effective and safe therapies. Here, inorganic–organic hybrid nanoparticles (GMP-IOH-NPs) are presented as a novel drug-delivery system for the selective delivery of extraordinarily high concentrations of gemcitabine monophosphate (GMP), not only to the primary tumor but also to metastatic sites. GMP-IOH-NPs have a composition of [ZrO]$^{2+}$[GMP]$^{2−}$ with GMP as drug anion (76% of total IOH-NP mass). Multiscale fluorescence imaging confirms an efficient uptake in tumor cells, independent of the activity of the human-equilibrative-nucleoside transporter (hENT1), being responsible for gemcitabine (GEM) transport into cells and a key factor for GEM resistance. Delivering already phosphorylated GMP via GMP-IOH-NPs into tumor cells also allows the cellular resistance induced by the downregulation of deoxycytidine kinase to be overcome. GMP-IOH-NPs show high accumulation in tumor lesions and only minor liver trapping when given intraperitoneally. GMP-IOH-NPs result in a higher antitumor efficacy compared to free GEM, which is further enhanced applying cetuximab-functionalized GMP-CTX-IOH-NPs. ... mehr


Verlagsausgabe §
DOI: 10.5445/IR/1000163621
Veröffentlicht am 31.10.2023
Originalveröffentlichung
DOI: 10.1002/adma.202305151
Scopus
Zitationen: 9
Web of Science
Zitationen: 9
Dimensions
Zitationen: 11
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Anorganische Chemie (AOC)
Institut für Biologische Grenzflächen (IBG)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2023
Sprache Englisch
Identifikator ISSN: 0935-9648, 1521-4095
KITopen-ID: 1000163621
HGF-Programm 43.33.11 (POF IV, LK 01) Adaptive and Bioinstructive Materials Systems
Erschienen in Advanced Materials
Verlag John Wiley and Sons
Band 35
Heft 46
Seiten Art.-Nr.: 2305151
Vorab online veröffentlicht am 16.08.2023
Schlagwörter chemoresistance, drug delivery, gemcitabine, inorganic–organic hybrid nanoparticles, metastasis, optical imaging, pancreatic cancer
Nachgewiesen in Web of Science
Dimensions
Scopus
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