A Macromolecular Drug for Cancer Therapy via Extracellular Calcification
Ning Tang
Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009 China
Institute of Translational Medicine, Zhejiang University, Hangzhou, 310029 China
Search for more papers by this authorHanhui Li
Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009 China
Institute of Translational Medicine, Zhejiang University, Hangzhou, 310029 China
Search for more papers by this authorLihong Zhang
Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009 China
Department of Biochemistry, Zhejiang University School of Medicine, Hangzhou, 310058 China
Search for more papers by this authorXueyun Zhang
Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009 China
Department of Biochemistry, Zhejiang University School of Medicine, Hangzhou, 310058 China
Search for more papers by this authorYanni Chen
Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009 China
Institute of Translational Medicine, Zhejiang University, Hangzhou, 310029 China
Search for more papers by this authorHao Shou
Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009 China
Institute of Translational Medicine, Zhejiang University, Hangzhou, 310029 China
Search for more papers by this authorShuaishuai Feng
Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009 China
Institute of Translational Medicine, Zhejiang University, Hangzhou, 310029 China
Search for more papers by this authorXinhua Chen
Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation Ministry of Public Health, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310003 China
Search for more papers by this authorProf. Dr. Yan Luo
Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009 China
Department of Biochemistry, Zhejiang University School of Medicine, Hangzhou, 310058 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Ruikang Tang
Department of Chemistry, Zhejiang University, Hangzhou, 310027 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Ben Wang
Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009 China
Institute of Translational Medicine, Zhejiang University, Hangzhou, 310029 China
Search for more papers by this authorNing Tang
Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009 China
Institute of Translational Medicine, Zhejiang University, Hangzhou, 310029 China
Search for more papers by this authorHanhui Li
Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009 China
Institute of Translational Medicine, Zhejiang University, Hangzhou, 310029 China
Search for more papers by this authorLihong Zhang
Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009 China
Department of Biochemistry, Zhejiang University School of Medicine, Hangzhou, 310058 China
Search for more papers by this authorXueyun Zhang
Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009 China
Department of Biochemistry, Zhejiang University School of Medicine, Hangzhou, 310058 China
Search for more papers by this authorYanni Chen
Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009 China
Institute of Translational Medicine, Zhejiang University, Hangzhou, 310029 China
Search for more papers by this authorHao Shou
Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009 China
Institute of Translational Medicine, Zhejiang University, Hangzhou, 310029 China
Search for more papers by this authorShuaishuai Feng
Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009 China
Institute of Translational Medicine, Zhejiang University, Hangzhou, 310029 China
Search for more papers by this authorXinhua Chen
Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation Ministry of Public Health, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310003 China
Search for more papers by this authorProf. Dr. Yan Luo
Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009 China
Department of Biochemistry, Zhejiang University School of Medicine, Hangzhou, 310058 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Ruikang Tang
Department of Chemistry, Zhejiang University, Hangzhou, 310027 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Ben Wang
Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009 China
Institute of Translational Medicine, Zhejiang University, Hangzhou, 310029 China
Search for more papers by this authorAbstract
Cancer chemotherapy typically relies on drug endocytosis and inhibits tumor cell proliferation via intracellular pathways; however, severe side effects may arise. In this study, we performed a first attempt to develop macromolecular-induced extracellular chemotherapy involving biomineralization by absorbing calcium from the blood through a new type of drug, polysialic acid conjugated with folate (folate-polySia), which selectively induces biogenic mineral formation on tumor cells and results in the pathological calcification of tumors. The macromolecule-initiated extracellular calcification causes cancer cell death mainly by intervening with the glycolysis process in cancer cells. Systemic administration of folate-polySia inhibited cervical and breast tumor growth and dramatically improved survival rates in mice. This study provides an extracellular therapeutic approach for malignant tumor diseases via calcification that is ready for clinical trials and offers new insights into macromolecular anticancer drug discovery.
Conflict of interest
The authors declare no conflict of interest.
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