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A nuclear permeable Ru(ii)-based photoactivated chemotherapeutic agent towards a series of cancer cells: in vitro and in vivo studies.
Dalton Trans. 2019 May 15; 48(19):6492-6500.DT

Abstract

Ru(ii) polypyridyl complexes which can undergo photo-induced ligand dissociation and DNA covalent binding are considered as potential photoactivated chemotherapeutic (PACT) agents. Herein four pyridine-2-sulfonate (py-SO3-) ligand based Ru(ii) complexes [Ru(N-N)2(py-SO3)]+ (1-4) were synthesized and studied. All the complexes can undergo fast py-SO3- ligand dissociation and DNA covalent binding upon visible light irradiation. However, only complex 4 exhibited high photo-induced anticancer activities towards a series of cancer cells, with half maximal inhibitory concentration (IC50) values in 100-300 nM regions and phototoxicity index (PI) values of about 100. In particular, complex 4 can also kill cisplatin resistant SKOV-3 and A549 cancer cells with IC50 values in 200-400 nM regions and PI values of about 50, which should be the first report of Ru(ii) based PACT agents that are also effective towards cisplatin resistant cancer cells. Complex 4 exhibited much higher cell uptake and nuclear accumulation levels, which may be the main reasons for its high anticancer activities. The in vivo anticancer experiments indicated that complex 4 can inhibit tumor growth significantly with fewer side effects. Our results may provide guidelines for developing novel photoactivatable Ru(ii) anticancer agents.

Authors+Show Affiliations

Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China. xswang@mail.ipc.ac.cn zhouqianxiong@mail.ipc.ac.cn.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30994660

Citation

Tian, Na, et al. "A Nuclear Permeable Ru(ii)-based Photoactivated Chemotherapeutic Agent Towards a Series of Cancer Cells: in Vitro and in Vivo Studies." Dalton Transactions (Cambridge, England : 2003), vol. 48, no. 19, 2019, pp. 6492-6500.
Tian N, Feng Y, Sun W, et al. A nuclear permeable Ru(ii)-based photoactivated chemotherapeutic agent towards a series of cancer cells: in vitro and in vivo studies. Dalton Trans. 2019;48(19):6492-6500.
Tian, N., Feng, Y., Sun, W., Lu, J., Lu, S., Yao, Y., Li, C., Wang, X., & Zhou, Q. (2019). A nuclear permeable Ru(ii)-based photoactivated chemotherapeutic agent towards a series of cancer cells: in vitro and in vivo studies. Dalton Transactions (Cambridge, England : 2003), 48(19), 6492-6500. https://doi.org/10.1039/c9dt00441f
Tian N, et al. A Nuclear Permeable Ru(ii)-based Photoactivated Chemotherapeutic Agent Towards a Series of Cancer Cells: in Vitro and in Vivo Studies. Dalton Trans. 2019 May 15;48(19):6492-6500. PubMed PMID: 30994660.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A nuclear permeable Ru(ii)-based photoactivated chemotherapeutic agent towards a series of cancer cells: in vitro and in vivo studies. AU - Tian,Na, AU - Feng,Yang, AU - Sun,Weize, AU - Lu,Jian, AU - Lu,Songsong, AU - Yao,Yishan, AU - Li,Chao, AU - Wang,Xuesong, AU - Zhou,Qianxiong, PY - 2019/4/18/pubmed PY - 2019/9/4/medline PY - 2019/4/18/entrez SP - 6492 EP - 6500 JF - Dalton transactions (Cambridge, England : 2003) JO - Dalton Trans VL - 48 IS - 19 N2 - Ru(ii) polypyridyl complexes which can undergo photo-induced ligand dissociation and DNA covalent binding are considered as potential photoactivated chemotherapeutic (PACT) agents. Herein four pyridine-2-sulfonate (py-SO3-) ligand based Ru(ii) complexes [Ru(N-N)2(py-SO3)]+ (1-4) were synthesized and studied. All the complexes can undergo fast py-SO3- ligand dissociation and DNA covalent binding upon visible light irradiation. However, only complex 4 exhibited high photo-induced anticancer activities towards a series of cancer cells, with half maximal inhibitory concentration (IC50) values in 100-300 nM regions and phototoxicity index (PI) values of about 100. In particular, complex 4 can also kill cisplatin resistant SKOV-3 and A549 cancer cells with IC50 values in 200-400 nM regions and PI values of about 50, which should be the first report of Ru(ii) based PACT agents that are also effective towards cisplatin resistant cancer cells. Complex 4 exhibited much higher cell uptake and nuclear accumulation levels, which may be the main reasons for its high anticancer activities. The in vivo anticancer experiments indicated that complex 4 can inhibit tumor growth significantly with fewer side effects. Our results may provide guidelines for developing novel photoactivatable Ru(ii) anticancer agents. SN - 1477-9234 UR - https://www.unboundmedicine.com/medline/citation/30994660/A_nuclear_permeable_Ru_ii__based_photoactivated_chemotherapeutic_agent_towards_a_series_of_cancer_cells:_in_vitro_and_in_vivo_studies_ L2 - https://doi.org/10.1039/c9dt00441f DB - PRIME DP - Unbound Medicine ER -