The living organisms produce organic-inorganic hybrid compounds to support their physiological activities, which is referred to as biomineralization. Notably, mineralization detected in specific tumor types after radiotherapy or chemotherapy has been proved to be associated with excellent prognostic. Therefore, it has emerged as a promising strategy to induce mineralization employing biomaterials to inhibit tumor progression. However, the modest ion-chelating capability of reported carboxyl-containing biomineralization initiators generates deficient tumor encapsulation, thus compromising the effect of tumor inhibition. Herein, a biomineralization-inducing nanoparticle (BINP) is designed for the blockade therapy of osteosarcoma, which is composed of dodecylamine-poly((γ-dodecyl-L-glutamate)-co-(L-histidine))-block-poly(L-glutamate-graft-alendronate), including membrane-insertion moiety, tumor microenvironment (TME)-responsive moiety, and mineralization-initiating moiety. After intravenous injection into mice bearing osteosarcoma, the histidine residue reacts to acidic TME to expose dodecyl group on the surface of expanded BINP, facilitating its membrane insertion. Subsequently, the protruding bisphosphonic acid groups on the cell surface trigger continuous ion deposition to construct mineralized barriers around the tumor. The potent mineral barriers block the exchange of substances between the tumor and surrounding normal tissues, resulting in effective primary osteosarcoma suppression and pulmonary metastasis remission simultaneously. Moreover, BINP administration mitigates bone destruction because of the suppression of alendronate to osteoclasts. Hence, the BINP-mediated biomineralization therapy shows a promising prospect for further clinical application in osteosarcoma therapy.

Acidity-triggered transformable polypeptide self-assembly to initiate tumor-specific biomineralization

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