Lactolytic and TGFβ-inhibiting nanoplatform overcomes immunosuppression to enhance radiosensitivity in osteosarcoma
Year: 2025
Type: article
Abstract: Osteosarcoma, the most prevalent malignant bone tumor in adolescents, presents significant clinical challenges due to its aggressive nature and resistance to conventional therapies including radiotherapy. Through analysis of human osteosarcoma specimens, we identified lactate and TGFβ as key regulators of the tumor microenvironment (TME), which collectively induce an immunosuppressive osteosarcoma microenvironment. To address this, we developed a novel multifunctional nanosystem constructed by genetically engineering lactate oxidase (LOX)-anchored platelet membranes to encapsulate manganese dioxide (MnO 2 ) nanoparticles and the TGFβ inhibitor SB525334. This system demonstrates tumor-selective accumulation while simultaneously enabling lactate catabolism and TGFβ suppression. In vitro and in vivo studies confirmed that this synergistic approach effectively inhibits TGFβ-mediated signaling pathways and enhances T cell-mediated anti-tumor immunity. Furthermore, combination therapy with PD-L1 blockade significantly suppressed tumor growth and reduced recurrence rates, demonstrating robust adaptive immune responses. These findings highlight the transformative potential of engineered platelet membrane nanosystems in integrating metabolic modulation with immune regulation to improve current osteosarcoma treatment paradigms.
Source: Nano Today
Authors: Linbang Wang, Jiaruo Tang, Rui Dou, Heng Zhang, Xiaomeng Cai, Yu Liu, Jingkun Liu, Xiaoguang Liu, Jiayu Zhang, Jun Chen
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,830
OpenAlex ID: W7111069616