TY - JOUR
T1 - A Multi-action and Multi-target RuII–PtIV Conjugate Combining Cancer-Activated Chemotherapy and Photodynamic Therapy to Overcome Drug Resistant Cancers
AU - Karges, Johannes
AU - Yempala, Thirumal
AU - Tharaud, Mickaël
AU - Gibson, Dan
AU - Gasser, Gilles
N1 - Publisher Copyright:
© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2020/4/27
Y1 - 2020/4/27
N2 - PtII complexes are commonly used to treat cancer. To reduce their side effects and improve their pharmacological properties, PtIV complexes are being developed as prodrug candidates that are activated by reduction in cancer cells. Concomitantly, RuII polypyridine complexes have gained much attention as photosensitizers for use in photodynamic therapy due to their attractive characteristics. In this article, a novel PtIV–RuII conjugate, which combines cancer activated chemotherapy with PDT, is presented. Upon entering the cancer cell, the PtIV centre is reduced to PtII and the axial ligands including the RuII complex and phenylbutyrate are released. As each component has its individual targets, the conjugate exerts a multi-target and multi-action effect with (photo-)cytotoxicity values upon irradiation up to 595 nm in the low nanomolar range in various (drug resistant) 2D monolayer cancer cells and 3D multicellular tumour spheroids.
AB - PtII complexes are commonly used to treat cancer. To reduce their side effects and improve their pharmacological properties, PtIV complexes are being developed as prodrug candidates that are activated by reduction in cancer cells. Concomitantly, RuII polypyridine complexes have gained much attention as photosensitizers for use in photodynamic therapy due to their attractive characteristics. In this article, a novel PtIV–RuII conjugate, which combines cancer activated chemotherapy with PDT, is presented. Upon entering the cancer cell, the PtIV centre is reduced to PtII and the axial ligands including the RuII complex and phenylbutyrate are released. As each component has its individual targets, the conjugate exerts a multi-target and multi-action effect with (photo-)cytotoxicity values upon irradiation up to 595 nm in the low nanomolar range in various (drug resistant) 2D monolayer cancer cells and 3D multicellular tumour spheroids.
KW - bioinorganic chemistry
KW - metals in medicine
KW - photodynamic therapy
KW - platinum prodrugs
UR - http://www.scopus.com/inward/record.url?scp=85081330898&partnerID=8YFLogxK
U2 - 10.1002/anie.201916400
DO - 10.1002/anie.201916400
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C2 - 32017379
AN - SCOPUS:85081330898
SN - 1433-7851
VL - 59
SP - 7069
EP - 7075
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 18
ER -