Versatile Polymer‐Initiating Biomineralization for Tumor Blockade Therapy

Abstract Tumor blockade therapy is a promising penetration‐independent antitumor modality, which effectively inhibits the exchange of nutrients, oxygen, and information between the tumor and surrounding microenvironments. However, the current blockade therapy strategies have limited antitumor efficacy due to defects of inadequate tumor obstruction, possible side effects, and short duration. For these reasons, a facilely synthesized versatile polymer 1,2‐distearoyl‐ sn ‐glycero‐3‐phosphoethanolamine– N ‐poly(ethylene glycol)–alendronate (DSPE‐PEG‐ALN, DPA) is developed to initiate the formation of biomineral shell around osteosarcoma as a potent physical barrier. The DSPE moiety shares a similar chemical structure with the cytomembrane, allowing the membrane insertion of DPA. The bisphosphonic acid groups in ALN attract ions to realize biomineralization around cells. After injection in the invasive osteosarcoma tissue, DPA inserts into the cytomembrane, induces continuous mineral deposition, and ultimately builds a physical barrier around the tumor. Meanwhile, ALN in DPA alleviates bone destruction by suppressing the activity of osteoclasts. Through hindering the exchange of necessary substances, the biomineralization coating inhibits the growth of primary osteosarcoma and pulmonary metastasis simultaneously. Therefore, the multifunctional polymer‐initiating blockade therapy provides a promising modality for tumor inhibition in clinics with high efficacy and negligible side effects.