Combinatorial Photothermal 3D-Printing Scaffold and Checkpoint Blockade Inhibits Growth/Metastasis of Breast Cancer to Bone and Accelerates Osteogenesis

Cancer metastases are the main causes for the high mortality of cancer. The current treatment modality for bone metastasis of breast cancer is dominantly destructive, which urges the engineering of multifunctional biomaterials, not only for eliminating primary/metastases tumors effectively but also for enhancing bone-tissue regeneration. Herein, an immune adjuvant (R837)-loaded and niobium carbide (Nb2C) MXene-modified 3D-printing biodegradable scaffold (BG@NbSiR) is designed and constructed to effectively treat bone metastasis of breast cancer. The engineered BG@NbSiR scaffold can eradicate primary tumors, activate the immune response, suppress metastases, prevent tumor relapses (long-term immunological memory) by synergizing with checkpoint blockade immunotherapy, and accelerate osteogenesis as evidenced by multiple in vivo murine models. In particular, single-cell sequencing (scRNA-seq) is employed to further determine the critical factors responding to BG@NbSiR scaffold-based photothermia plus checkpoint blockade-combined immunotherapy. Several gene functional terms are identified in both tumor biology (including copy number variation) and immune response, which further reveal the underlying therapeutic mechanisms from the perspective of single-cell transcriptome. This work not only demonstrates the promising clinical application potentials of BG@NbSiR scaffold-based therapy against bone metastasis of breast cancer, but also provides distinctive avenues to optimize the design and construction of multifunctional tissue-engineering biomaterials based on single-cell genomes.