Glycoengineering-assistant biomineralization for tumor blockade therapy

Tumor blockade therapy inhibits tumor progression by cutting off essential supplies of nutrients, oxygen, and biomolecules from the surrounding microenvironment. Inspired by natural processes, tumor biomineralization has evolved due to its biocompatibility, self-reinforcing capability, and penetration-independent mechanism. However, the selective induction of tumor biomineralization using synthetic tools presents a significant challenge. Herein, a metabolic glycoengineering-assistant tumor biomineralization strategy was developed. Specifically, the azido group (N3) was introduced onto the cytomembrane by incubating tumor cells with glycose analog Ac4ManNAz. In addition, a bisphosphonate-containing polymer, dibenzocyclooctyne-poly(ethylene glycol)-alendronate (DBCO-PEG-ALN, DBPA) was synthesized, which attached to the tumor cell surface via "click chemistry" reaction between DBCO and N3. Subsequently, the bisphosphonate group on the cell surface chelated with positively charged ions in the microenvironment, triggering a consecutive process of biomineralization. This physical barrier significantly reduced tumor cell viability and mobility in a calcium ion concentration-dependent manner, suggesting its potential as an effective anti-tumor strategy for in vivo applications.