Tetrahedral Framework Nucleic Acid-Loaded Retinoic Acid Promotes Osteosarcoma Stem Cell Clearance

• Published in: ACS applied materials & interfaces 2024-10, Vol.16 (43), p.58452-58463
• Main Authors: Zhang, Weifei, Li, Mengqing, Zhao, Zhen, Xu, Jiangshan, Liu, Junlin, Feng, Pin, Zhang, Bin, Huang, Zhangheng, Kong, Qing-Quan, Lin, Yunfeng
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and Medical Applications of Materials and Interfaces; Bone Neoplasms - drug therapy; Bone Neoplasms - metabolism; Bone Neoplasms - pathology; Cell Line, Tumor; Drug Carriers - chemistry; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles - chemistry; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Nucleic Acids - chemistry; Nucleic Acids - pharmacology; Osteosarcoma - drug therapy; Osteosarcoma - metabolism; Osteosarcoma - pathology; Tretinoin - chemistry; Tretinoin - pharmacology
• ISSN: 1944-8244; 1944-8252; 1944-8252
• DOI: 10.1021/acsami.4c14440

Metastatic osteosarcoma is a commonly seen malignant tumor in adolescents, with a five year survival rate of approximately 20% and a lack of treatment options. Osteosarcoma cancer stem cells are considered to be important drivers of the metastasis of osteosarcoma, and therefore their clearance is considered a promising strategy for treating metastatic osteosarcoma. In the relevant literature, retinoic acid (ATRA) is considered effective for eliminating osteosarcoma stem cells, but it has some inherent disadvantages, including poor solubility, difficulty in entering cells, and structural instability. Tetrahedral framework nucleic acids (tFNAs) are a type of nanoparticles that can carry small-molecule drugs into cells to exert therapeutic effects. Therefore, we designed and synthesized a nanoparticle named T-ATRA by using tFNAs to load ATRA and studied its effect in a nude mouse model. T-ATRA is more effective than ATRA in the clearance of osteosarcoma stem cells and in inhibiting osteosarcoma cell metastasis via the Wnt signaling pathway, thus prolonging the survival time of nude mice with osteosarcoma.