A Macromolecular Drug for Cancer Therapy via Extracellular Calcification

Abstract

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.

Versatile Polymer‐Initiating Biomineralization for Tumor Blockade Therapy

“…As shown in Figure 1D and Figure S7, Supporting Information, the green fluorescence of the biomineral layer stained by calcein co‐localized with the red fluorescence of cancer cell membrane in the DPA and DPAC groups. [ 13 ] In sharp contrast, there was no apparent green fluorescence in the Control or Ca group. To further confirm the deposition of Ca, we observed 143B cells in different groups through scanning electron microscopy (SEM).…”

Prussian Blue/Calcium Peroxide Nanocomposites-Mediated Tumor Cell Iron Mineralization for Treatment of Experimental Lung Adenocarcinoma

“…These observations imply that calcification of a tumor may have a positive effect on the inhibition of tumor cell proliferation, resulting in a therapeutic effect on tumors. Inspired by this, we proposed a cancer-cell-targeting calcification strategy and achieved tumor calcification spontaneously to inhibit tumor growth and metastasis induced by polycarboxylic macromolecules, , which is similar to the formation of hard tissue in living bodies, such as the physiological formation of bone and teeth. However, our pilot study implied that artificial tumor calcification showed limited tumor-inhibiting ability, as the speed of calcification is quite low, , which also impairs the ability of tumor calcification to prevent tumor metastasis.…”

“…Inspired by this, we proposed a cancer-cell-targeting calcification strategy and achieved tumor calcification spontaneously to inhibit tumor growth and metastasis induced by polycarboxylic macromolecules, , which is similar to the formation of hard tissue in living bodies, such as the physiological formation of bone and teeth. However, our pilot study implied that artificial tumor calcification showed limited tumor-inhibiting ability, as the speed of calcification is quite low, , which also impairs the ability of tumor calcification to prevent tumor metastasis. Moreover, the slow calcification process cannot induce effective tumor calcification points for medical imaging in a relatively short time, which also limits its effectiveness of tumor diagnosis.…”

CaCO3‐Encapuslated Microspheres for Enhanced Transhepatic Arterial Embolization Treatment of Hepatocellular Carcinoma

“…[60] Excessive Ca 2+ can cause extracellular calcification that causes cancer cell death. [61] We also explored the effect of Ca 2+ on the proliferation, invasion, and migration of HCC cells in vitro via colony formation assay, transwell assay, and wound healing assay. The results were displayed in Figure S2 in the Supporting Information.…”