Sodium alginate hydrogel loaded with upconversion nanoparticles and magnesium ions enhances bone regeneration and photodynamic tumor therapy

Siyu Song ^1,2 Xirao Sun ^1,2 Yanfu Wang ³ Meng Wang ^1,2 Zheng Shi ^1,2 Danfang Sun ^1,2 Dan Li ^1,2 Jianduo Chen ^1,2 Chengyue Wang ^1,2,4*

• ¹ 锦州医科大学附属口腔医院, 锦州市, China
• ² Jinzhou Medical University School of Stomatology, Jinzhou, China
• ³ School of Stomatology, China Medical University, Shenyang, Liaoning Province, China
• ⁴ Collaborative Innovation Center for Health Promotion of Children and Adolescents of Jinzhou Medical University, Jinzhou, China

Oral squamous cell carcinoma (OSCC) usually invades the jawbone over the course of the disease. Hence, it is necessary to consider the treatment of the tumor and repair of the jawbone, and the treatment process is very complicated. However, conventional therapy for OSCC mainly emphasizes tumor removal, which often fails to address the repair of jawbone defects and destroys residual tumor cells after treatment. In this study, a sodium alginate-upconversion nanoparticle (UCNP)-magnesium particle composite hydrogel platform (SUMg) was designed to promote bone regeneration and facilitate tumor cell death. In vitro, SUMg exhibited high cytocompatibility and promoted cell viability, proliferation, spreading, and osteogenesis owing to the incorporation of MPs, with SU10Mg having the most significant effect. Among UCNPs, we selected NaYF4. NaYF4, folic acid, and chlorin e6 were combined on the surface for modification to prepare UFC. Folic acid on the surface enhanced uptake by OSCC cells. Under 980 nm laser irradiation, the red emission of Er 3+ could be excited. This triggered chlorin e6, which induced a photodynamic therapy effect and destroyed surviving tumor cells. In vivo experiments further confirmed that SU10Mg could promote bone regeneration, and under 980 nm near-infrared irradiation, the UFC produced local reactive oxygen species in the tumor within 5 min. In summary, the composite hydrogel platform not only promotes bone formation but also destroy tumor cell residues, providing a new approach for the treatment of OSCC.