A Macromolecular Drug for Cancer Therapy via Extracellular Calcification

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 a...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2021-03, Vol.60 (12), p.6509-6517
Main Authors: Tang, Ning, Li, Hanhui, Zhang, Lihong, Zhang, Xueyun, Chen, Yanni, Shou, Hao, Feng, Shuaishuai, Chen, Xinhua, Luo, Yan, Tang, Ruikang, Wang, Ben
Format: Article
Language:English
Subjects:
antitumor therapy
biomineralization
Breast cancer
Calcification
Calcium
Calcium (blood)
Cancer
Cancer therapies
Cell death
Cell proliferation
Cervix
Chemotherapy
Clinical trials
Endocytosis
Folic acid
Glycolysis
macromolecular drug
Macromolecules
Mineralization
Polysialic acid
Side effects
Survival
Tumor cells
Tumors
Vitamin B
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Summary: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. We propose a macromolecular‐drug‐induced extracellular chemotherapy involving biomineralization by absorbing calcium from blood. Polysialic acid combined with folate, which spontaneously induces biogenic mineral formation on cancer cells rich in folate receptors, leads to targeted pathological calcification and cell death. Systemic administration of folate‐polySia improves survival rates of tumor‐bearing mice with negligible side effects.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202016122