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Targeted Management of Diabetic Osteoporosis by Biocatalytic Cascade Reaction Nanoplatform
Lian-Hua Fu1, Mengting Yin2, Xin Chen1
1Marshall Laboratory of Biomedical Engineering, International Cancer Center, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong 518055, China.
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 PO43- can stimulate osteogenesis and suppress osteoclastogenesis, thereby hastening bone formation and reversing osteoporosis. This nanoplatform shows promise in managing DOP both in vitro and in vivo. Our findings open a new horizon for managing DOP through biocatalytic cascade reactions.

