Department of Joint and Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, PR China; Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, PR China.
Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, PR China.
Int J Biol Macromol. 2024 Jun;270(Pt 2):132029. doi: 10.1016/j.ijbiomac.2024.132029. Epub 2024 May 3.
Cuproptosis affects osteosarcoma locally, and the exploitation of cuproptosis-related biomaterials for osteosarcoma treatment is still in its infancy. We designed and synthesized a novel injectable gel of Cu ion-coordinated Tremella fuciformis polysaccharide (TFP-Cu) for antiosteosarcoma therapy. This material has antitumor effects, the ability to stimulate immunity and promote bone formation, and a controlled Cu release profile in smart response to tumor microenvironment stimulation. TFP-Cu can selectively inhibit the proliferation of K7M2 tumor cells by arresting the cell cycle and promoting cell apoptosis and cuproptosis. TFP-Cu also promoted the M1 polarization of RAW264.7 cells and regulated the immune microenvironment. These effects increased osteogenic gene and protein expression in MC3T3-E1 cells. TFP-Cu could significantly limit tumor growth in tumor-bearing mice by inducing tumor cell apoptosis and improving the activation of anti-CD8 T cell-mediated immune responses. Therefore, TFP-Cu could be a potential candidate for treating osteosarcoma and bioactive drug carrier for further cancer-related applications.
铜死亡影响骨肉瘤局部，且利用铜死亡相关生物材料治疗骨肉瘤仍处于起步阶段。我们设计并合成了一种新型的铜离子配位银耳多糖（TFP-Cu）可注射水凝胶，用于抗骨肉瘤治疗。该材料具有抗肿瘤作用、刺激免疫和促进骨形成的能力，并能智能响应肿瘤微环境刺激，控制铜的释放。TFP-Cu 通过阻滞细胞周期和促进细胞凋亡和铜死亡，选择性抑制 K7M2 肿瘤细胞的增殖。TFP-Cu 还促进了 RAW264.7 细胞的 M1 极化，并调节了免疫微环境。这些作用增加了 MC3T3-E1 细胞中成骨基因和蛋白的表达。TFP-Cu 通过诱导肿瘤细胞凋亡和改善抗 CD8 T 细胞介导的免疫反应激活，显著抑制荷瘤小鼠肿瘤生长。因此，TFP-Cu 可能是治疗骨肉瘤的潜在候选药物，也是用于进一步癌症相关应用的生物活性药物载体。
