Bioconjugation of Supramolecular Metallacages to Integrin Ligands for Targeted Delivery of Cisplatin
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Bioconjugation of Supramolecular Metallacages to Integrin Ligands for Targeted Delivery of Cisplatin. / Han, Jiaying; Räder, Andreas F B; Reichart, Florian; Aikman, Brech; Wenzel, Margot N; Woods, Ben; Weinmüller, Michael; Ludwig, Beatrice S; Stürup, Stefan; Groothuis, Geny M M; Permentier, Hjalmar P; Bischoff, Rainer; Kessler, Horst; Horvatovich, Peter; Casini, Angela.
I: Bioconjugate Chemistry, Bind 29, Nr. 11, 21.11.2018, s. 3856-3865.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Bioconjugation of Supramolecular Metallacages to Integrin Ligands for Targeted Delivery of Cisplatin
AU - Han, Jiaying
AU - Räder, Andreas F B
AU - Reichart, Florian
AU - Aikman, Brech
AU - Wenzel, Margot N
AU - Woods, Ben
AU - Weinmüller, Michael
AU - Ludwig, Beatrice S
AU - Stürup, Stefan
AU - Groothuis, Geny M M
AU - Permentier, Hjalmar P
AU - Bischoff, Rainer
AU - Kessler, Horst
AU - Horvatovich, Peter
AU - Casini, Angela
PY - 2018/11/21
Y1 - 2018/11/21
N2 - Cisplatin occupies a crucial role in the treatment of various malignant tumors. However, its efficacy and applicability are heavily restricted by severe systemic toxicities and drug resistance. Our study exploits the active targeting of supramolecular metallacages to enhance the activity of cisplatin in cancer cells while reducing its toxicity. Thus, Pd2L4 cages (L = ligand) have been conjugated to four integrin ligands with different binding affinity and selectivity. Cage formation and encapsulation of cisplatin was proven by NMR spectroscopy. Upon encapsulation, cisplatin showed increased cytotoxicity in vitro, in melanoma A375 cells overexpressing αvβ3 integrins. Moreover, ex vivo studies in tissue slices indicated reduced toxicity toward healthy liver and kidney tissues for cage-encapsulated cisplatin. Analysis of metal content by ICP-MS demonstrated that the encapsulated drug is less accumulated in these organs compared to the "free" cisplatin.
AB - Cisplatin occupies a crucial role in the treatment of various malignant tumors. However, its efficacy and applicability are heavily restricted by severe systemic toxicities and drug resistance. Our study exploits the active targeting of supramolecular metallacages to enhance the activity of cisplatin in cancer cells while reducing its toxicity. Thus, Pd2L4 cages (L = ligand) have been conjugated to four integrin ligands with different binding affinity and selectivity. Cage formation and encapsulation of cisplatin was proven by NMR spectroscopy. Upon encapsulation, cisplatin showed increased cytotoxicity in vitro, in melanoma A375 cells overexpressing αvβ3 integrins. Moreover, ex vivo studies in tissue slices indicated reduced toxicity toward healthy liver and kidney tissues for cage-encapsulated cisplatin. Analysis of metal content by ICP-MS demonstrated that the encapsulated drug is less accumulated in these organs compared to the "free" cisplatin.
U2 - 10.1021/acs.bioconjchem.8b00682
DO - 10.1021/acs.bioconjchem.8b00682
M3 - Journal article
C2 - 30380298
VL - 29
SP - 3856
EP - 3865
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
SN - 1043-1802
IS - 11
ER -
ID: 222166267