(W1077) NOVEL POSTOPERATIVE TREATMENT STRATEGY FOR OSTEOSARCOMA: INTEGRATED APPROACH OF PHOTOTHERMAL IMMUNOTHERAPY WITH BONE REGENERATION BASED ON INJECTABLE HYDROGEL

Abstract: Osteosarcoma is the most common primary malignant bone tumor. Current treatments, including surgery and chemotherapy, have not significantly improved survival rates, and there is a high rate of recurrence. Surgery often results in large bone defects, and existing reconstruction methods are inadequate. This study proposes a new treatment approach that combines photothermal immunotherapy with autologous bone repair, utilizing a novel injectable thermosensitive hydrogel loaded with the immunomodulatory drug JQ1, the photothermal agent indocyanine green (ICG), and the bone repair agent nano-hydroxyapatite (nHAp).
In a postoperative mouse model of osteosarcoma, the combination of photothermal immunotherapy demonstrated significant tumor suppression, while neither treatment alone effectively inhibited tumor recurrence. Tumor samples were analyzed using single-cell RNA sequencing (scRNA-seq), revealing a unique immune microenvironment characterized by low lymphocyte counts and a predominance of myeloid cells, particularly tumor-associated macrophages (TAMs) with immunosuppressive properties. Pseudotime analysis traced the differentiation of Ly6c+ monocytes into M1 and M2 macrophages. The results indicated that photothermal therapy enhanced monocyte infiltration, while JQ1 promoted differentiation into M1 macrophages. The hydrogel containing nHAp exhibited significant osteogenic effects, with the inclusion of nHAp upregulating the expression of osteogenic genes and promoting osteogenic differentiation in MC3T3 cells. In a femoral defect model, micro-CT and histological analyses supported that nHAp significantly increased new bone formation, mineral density, and trabecular density at the defect site, effectively facilitating bone repair in mice.
This study provides a novel and efficient postoperative treatment method for osteosarcoma, integrating photothermal immunotherapy and bone regeneration, and evaluates the therapeutic effects at the molecular level, offering new insights for the treatment of osteosarcoma.

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