ZJU scientists develop macromolecular drug for cancer therapy via extracellular calcification

Cancer is one of the leading causes of mortality. Chemotherapy is still the most commonly used treatment for cancer patients. It typically relies on drug endocytosis and inhibits tumor cell proliferation via intracellular pathways. However, most chemotherapy drugs damage normal cells since they work by affecting the physiological processes of cell proliferation. The side effects of systemic chemotherapy used to treat cancer are often severe and may damage the tumor‐bearing host, especially the immune system. 

Calcification is observed in cancer. It has been reported that tumor calcification and calcification in regional lymph nodes can be thought of as a benign prognostic factor in colorectal cancer and lung cancer. Promoting cancer cell calcification may become a novel approach to curing cancer. However, this way relies heavily on a high concentration of Ca²⁺. The abnormally high‐concentration calcium solution is likely to induce a hypercalcemia crisis, resulting in severe conditions such as cardiac arrest, which therefore inhibits its application in the clinic.

Inspired by biomineralization in nature, two Zhejiang University research teams conducted collaborative research into cancer therapy. They are led respectively by WANG Ben, an associate professor from the Institute of Translational Medicine and Prof. TANG Ruikang from the Department of Chemistry. Their research findings are published as a cover feature in the journal Angew. Chem. Int. Ed.

In their study, they developed a new polysaccharide‐based conjugate combining folate and polysialic acid (polySia), which can provide several carboxylate groups to enrich calcium from blood and induce cancer cell calcification spontaneously and selectively.The application of folate‐polySia can induce spontaneous and pathological calcification inside tumors, leading to successful tumor inhibition by affecting the aerobic glycolysis of cancer cells. The calcification induced by folate‐polySia does not require additional calcium supplementation. Thus, there is no risk of hypercalcemia. This approach produces an ideal anticancer effect with negligible side effects on the host compared with traditional chemotherapy drugs. 

“This study provides new insights into macromolecular drug development,” said WANG Ben. “It offers a new strategy of extracellular imprisonment and killing of cancer cells by polysaccharide‐induced calcification with blood calcium under physiological conditions that may improve the survival rate of patients with cancer.”