Is GSH Chelated Pt Molecule Inactive in Anti-Cancer Treatment? A Case Study of Pt6GS4
Chunyu Zhang
Department of Chemistry and Chemical Engineering, Beijing University of Technology, Beijing, 100124 P. R. China
Search for more papers by this authorCorresponding Author
Liang Gao
Department of Chemistry and Chemical Engineering, Beijing University of Technology, Beijing, 100124 P. R. China
E-mail: [email protected],[email protected]
Search for more papers by this authorQing Yuan
Department of Chemistry and Chemical Engineering, Beijing University of Technology, Beijing, 100124 P. R. China
Search for more papers by this authorLina Zhao
CAS Key Laboratory for the Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049 P. R. China
Search for more papers by this authorWenchao Niu
Department of Chemistry and Chemical Engineering, Beijing University of Technology, Beijing, 100124 P. R. China
Search for more papers by this authorPengju Cai
CAS Key Laboratory for the Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049 P. R. China
Search for more papers by this authorJiaojiao Li
Department of Chemistry and Chemical Engineering, Beijing University of Technology, Beijing, 100124 P. R. China
Search for more papers by this authorXu Han
CAS Key Laboratory for the Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049 P. R. China
Search for more papers by this authorZhesheng He
CAS Key Laboratory for the Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049 P. R. China
Search for more papers by this authorFuping Gao
CAS Key Laboratory for the Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049 P. R. China
Search for more papers by this authorYaling Wang
CAS Key Laboratory for the Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049 P. R. China
Search for more papers by this authorHuaidong Jiang
School of Physical Science and Technology, Shanghai Tech University, Shanghai, 201210 P. R. China
Search for more papers by this authorZhifang Chai
CAS Key Laboratory for the Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049 P. R. China
Search for more papers by this authorCorresponding Author
Xueyun Gao
Department of Chemistry and Chemical Engineering, Beijing University of Technology, Beijing, 100124 P. R. China
E-mail: [email protected],[email protected]
Search for more papers by this authorChunyu Zhang
Department of Chemistry and Chemical Engineering, Beijing University of Technology, Beijing, 100124 P. R. China
Search for more papers by this authorCorresponding Author
Liang Gao
Department of Chemistry and Chemical Engineering, Beijing University of Technology, Beijing, 100124 P. R. China
E-mail: [email protected],[email protected]
Search for more papers by this authorQing Yuan
Department of Chemistry and Chemical Engineering, Beijing University of Technology, Beijing, 100124 P. R. China
Search for more papers by this authorLina Zhao
CAS Key Laboratory for the Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049 P. R. China
Search for more papers by this authorWenchao Niu
Department of Chemistry and Chemical Engineering, Beijing University of Technology, Beijing, 100124 P. R. China
Search for more papers by this authorPengju Cai
CAS Key Laboratory for the Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049 P. R. China
Search for more papers by this authorJiaojiao Li
Department of Chemistry and Chemical Engineering, Beijing University of Technology, Beijing, 100124 P. R. China
Search for more papers by this authorXu Han
CAS Key Laboratory for the Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049 P. R. China
Search for more papers by this authorZhesheng He
CAS Key Laboratory for the Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049 P. R. China
Search for more papers by this authorFuping Gao
CAS Key Laboratory for the Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049 P. R. China
Search for more papers by this authorYaling Wang
CAS Key Laboratory for the Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049 P. R. China
Search for more papers by this authorHuaidong Jiang
School of Physical Science and Technology, Shanghai Tech University, Shanghai, 201210 P. R. China
Search for more papers by this authorZhifang Chai
CAS Key Laboratory for the Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049 P. R. China
Search for more papers by this authorCorresponding Author
Xueyun Gao
Department of Chemistry and Chemical Engineering, Beijing University of Technology, Beijing, 100124 P. R. China
E-mail: [email protected],[email protected]
Search for more papers by this authorAbstract
Platinum (Pt) drugs are widely used in anti-cancer treatment although many reports advocated that tumor cells could inactivate Pt drugs via glutathione-Pt (GSH-Pt) adducts formation. To date, GSH chelated Pt molecules have not been assessed in cancer treatment because GSH-Pt adducts are not capable of killing cancer cells, which is widely accepted and well followed. In this report, endogenous biothiol is utilized to precisely synthesize a GSH chelated Pt molecule (Pt6GS4). This Pt6GS4 molecule can be well taken up by aggressive triple negative breast cancer (TNBC) cells. Subsequently, its metabolites could enter nuclei to interact with DNA, finally the DNA-Pt complex triggers TNBC cell apoptosis via the p53 pathway. Impressively, high efficacy for anti-cancer treatment is achieved by Pt6GS4 both in vitro and in vivo when compared with traditional first-line carboplatin in the same dosage. Compared with carboplatin, Pt6GS4 keeps tumor bearing mice alive for a longer time and is non-toxic for the liver and kidneys. This work opens a route to explore polynuclear Pt compound with accurate architecture for enhancing therapeutic effects and reducing systemic toxicity.
Conflict of Interest
The authors declare no conflict of interest.
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