TY - JOUR
T1 - Silver Atomic Quantum Clusters of Three Atoms for Cancer Therapy: Targeting Chromatin Compaction to Increase the Therapeutic Index of Chemotherapy
AU - Barone, Giampaolo
AU - Carneiro, Carmen
AU - García, Begoña
AU - Leal, José Maria
AU - Blanco, M. Carmen
AU - Buceta, David
AU - Neissa, José
AU - Borgman, Kyra J. E.
AU - Domínguez, Blanca
AU - Huseyinova, Shahana
AU - Busto, Natalia
AU - Porto, Vanesa
AU - Borrajo, Erea
AU - Blanco, José
AU - Leal, José Maria
AU - Lakadamyali, Melike
AU - Garcia-Parajo, Maria F.
AU - García-Caballero, Tomás
AU - López-Quintela, M. Arturo
AU - Rivas, José
AU - Domínguez, Fernando
PY - 2018
Y1 - 2018
N2 - Nanomaterials with very low atomicity deserve consideration as potential pharmacological agents owing to their very small size and to their properties that can be precisely tuned with minor modifications to their size. Here, it is shown that silver clusters of three atoms (Ag3-AQCs)—developed by an ad hoc method—augment chromatin accessibility. This effect only occurs during DNA replication. Coadministration of Ag3-AQCs increases the cytotoxic effect of DNA-acting drugs on human lung carcinoma cells. In mice with orthotopic lung tumors, the coadministration of Ag3-AQCs increases the amount of cisplatin (CDDP) bound to the tumor DNA by fivefold without modifying CDDP levels in normal tissues. As a result, CDDP coadministered with Ag3-AQCs more strongly reduces the tumor burden. Evidence of the significance of targeting chromatin compaction to increase the therapeutic index of chemotherapy is now provided.
AB - Nanomaterials with very low atomicity deserve consideration as potential pharmacological agents owing to their very small size and to their properties that can be precisely tuned with minor modifications to their size. Here, it is shown that silver clusters of three atoms (Ag3-AQCs)—developed by an ad hoc method—augment chromatin accessibility. This effect only occurs during DNA replication. Coadministration of Ag3-AQCs increases the cytotoxic effect of DNA-acting drugs on human lung carcinoma cells. In mice with orthotopic lung tumors, the coadministration of Ag3-AQCs increases the amount of cisplatin (CDDP) bound to the tumor DNA by fivefold without modifying CDDP levels in normal tissues. As a result, CDDP coadministered with Ag3-AQCs more strongly reduces the tumor burden. Evidence of the significance of targeting chromatin compaction to increase the therapeutic index of chemotherapy is now provided.
KW - DNA-binding drugs
KW - Materials Science (all)
KW - Mechanical Engineering
KW - Mechanics of Materials
KW - atomic quantum clusters
KW - cancer therapy
KW - chromatin accessibility
KW - silver clusters
KW - DNA-binding drugs
KW - Materials Science (all)
KW - Mechanical Engineering
KW - Mechanics of Materials
KW - atomic quantum clusters
KW - cancer therapy
KW - chromatin accessibility
KW - silver clusters
UR - http://hdl.handle.net/10447/338539
UR - http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1521-4095
M3 - Article
VL - 30
SP - e1801317-
JO - Advanced Materials
JF - Advanced Materials
SN - 0935-9648
ER -