TY - JOUR
T1 - Ruthenium(II) polypyridyl complexes as mitochondria-targeted two-photon photodynamic anticancer agents
AU - Liu, Jiangping
AU - Chen, Yu
AU - Li, Guanying
AU - Zhang, Pingyu
AU - Jin, Chengzhi
AU - Zeng, Leli
AU - Ji, Liangnian
AU - Chao, Hui
N1 - Publisher Copyright:
© 2015 Elsevier Ltd.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - Clinical acceptance of photodynamic therapy is currently hindered by poor depth efficacy and inefficient activation of the cell death machinery in cancer cells during treatment. To address these issues, photoactivation using two-photon absorption (TPA) is currently being examined. Mitochondria-targeted therapy represents a promising approach to target tumors selectively and may overcome the resistance in current anticancer therapies. Herein, four ruthenium(II) polypyridyl complexes (RuL1-RuL4) have been designed and developed to act as mitochondria-targeted two-photon photodynamic anticancer agents. These complexes exhibit very high singlet oxygen quantum yields in methanol (0.74-0.81), significant TPA cross sections (124-198GM), remarkable mitochondrial accumulation, and deep penetration depth. Thus, RuL1-RuL4 were utilized as one-photon and two-photon absorbing photosensitizers in both monolayer cells and 3D multicellular spheroids (MCSs). These Ru(II) complexes were almost nontoxic towards cells and 3D MCSs in the dark and generate sufficient singlet oxygen under one- and two-photon irradiation to trigger cell death. Remarkably, RuL4 exhibited an IC50 value as low as 9.6μM in one-photon PDT (λirr=450nm, 12Jcm-2) and 1.9μM in two-photon PDT (λirr=830nm, 800Jcm-2) of 3D MCSs; moreover, RuL4 is an order of magnitude more toxic than cisplatin in the latter test system. The combination of mitochondria-targeting and two-photon activation provides a valuable paradigm to develop ruthenium(II) complexes for PDT applications.
AB - Clinical acceptance of photodynamic therapy is currently hindered by poor depth efficacy and inefficient activation of the cell death machinery in cancer cells during treatment. To address these issues, photoactivation using two-photon absorption (TPA) is currently being examined. Mitochondria-targeted therapy represents a promising approach to target tumors selectively and may overcome the resistance in current anticancer therapies. Herein, four ruthenium(II) polypyridyl complexes (RuL1-RuL4) have been designed and developed to act as mitochondria-targeted two-photon photodynamic anticancer agents. These complexes exhibit very high singlet oxygen quantum yields in methanol (0.74-0.81), significant TPA cross sections (124-198GM), remarkable mitochondrial accumulation, and deep penetration depth. Thus, RuL1-RuL4 were utilized as one-photon and two-photon absorbing photosensitizers in both monolayer cells and 3D multicellular spheroids (MCSs). These Ru(II) complexes were almost nontoxic towards cells and 3D MCSs in the dark and generate sufficient singlet oxygen under one- and two-photon irradiation to trigger cell death. Remarkably, RuL4 exhibited an IC50 value as low as 9.6μM in one-photon PDT (λirr=450nm, 12Jcm-2) and 1.9μM in two-photon PDT (λirr=830nm, 800Jcm-2) of 3D MCSs; moreover, RuL4 is an order of magnitude more toxic than cisplatin in the latter test system. The combination of mitochondria-targeting and two-photon activation provides a valuable paradigm to develop ruthenium(II) complexes for PDT applications.
KW - 3D multicellular spheroids
KW - Mitochondria
KW - Photodynamic therapy
KW - Ruthenium(II) complex
KW - Two-photon
UR - https://www.scopus.com/pages/publications/84928395653
U2 - 10.1016/j.biomaterials.2015.04.002
DO - 10.1016/j.biomaterials.2015.04.002
M3 - 文章
C2 - 25934287
AN - SCOPUS:84928395653
SN - 0142-9612
VL - 56
SP - 140
EP - 153
JO - Biomaterials
JF - Biomaterials
ER -
