Year: 2026
Type: article
Abstract: Osteosarcoma (OS) remains the most prevalent malignant bone tumor, with stagnant survival rates and high recurrence risk due to residual tumor cells, and limited post-resection bone regeneration. Existing bifunctional bone graft substitutes integrating anticancer activity with osteogenesis are hindered by uncontrolled drug release and inefficient intracellular delivery. Here, we report a pH-sensitive nano-microparticle linking strategy, in which imine bonds are used as interfacial linkers between therapeutic nanoparticles and bone scaffolds to enable tumor microenvironment-triggered, on-demand nanotherapeutic release. In this study, we develop β-tricalcium phosphate (β-TCP) granules decorated with selenium (Se)-doped mesoporous silica nanoparticles (SeMIA@TCP), in which nanoparticles are functionalized with imine bonds for acidic pH-responsive detachment and alendronate for strong β-TCP binding. This design ensures stable nanoparticle immobilization under physiological conditions while enabling selective release within the mildly acidic OS microenvironment. In vitro, the SeMIA@TCP showed significant pH-dependent cytotoxicity toward OS cells, while maintaining low toxicity toward human mesenchymal stem cells (hMSCs) under physiological conditions, indicating a OS-targeting profile. Furthermore, the released nanoparticles enhanced alkaline phosphatase (ALP) expression and mineralization in hMSCs, underscoring their osteogenic potential. Collectively, these results demonstrate the potential of tumor microenvironment-responsive Se-doped MSN-assembled TCP granules as a design platform for bifunctional scaffolds in bone cancer treatment.
Source: Small
Institution: Maastricht University
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $5,790
OpenAlex ID: W7129398135