Targeted Management of Diabetic Osteoporosis by Biocatalytic Cascade Reaction Nanoplatform.

Abstract

Diabetic osteoporosis (DOP) is a chronic complication of diabetes mellitus (DM) that impairs bone health, and effective management of DOP remains a formidable challenge. In this study, we developed a biocatalytic cascade nanoplatform, GOx@SrCaP-CAT-Tet, offering osteogenic, angiogenic, and anti-inflammatory activities for targeted DOP management. The platform includes glucose oxidase (GOx) and catalase (CAT), encapsulated in strontium-doped calcium phosphate (SrCaP), converting glucose into gluconic acid and hydrogen peroxide (H₂O₂), alleviating the hyperglycemia and promoting hypoxia-induced vascularization. Both the generated H₂O₂ and any overabundance of H₂O₂ in the DOP microenvironment can be scavenged by CAT, thus relieving inflammation. Via a surface modified with tetracycline (Tet) for bone targeting, the release of Sr²⁺, Ca²⁺, and PO₄^3- can stimulate osteogenesis and suppress osteoclastogenesis, thereby hastening bone formation and reversing osteoporosis. This nanoplatform shows promise in managing DOP both <i>in vitro</i> and <i>in vivo</i>. Our findings open a new horizon for managing DOP through biocatalytic cascade reactions.