Li Lin, Lin Yating, Liu Kun, Huang Runshan, Wen Wei, Huang Yadong, Liu Mingxian, Zhou Changren, Ding Shan, Luo Binghong
Biomaterial research laboratory, Department of Material Science and Engineering, College of Chemistry and Materials, Jinan University, Guangzhou, 510632, P. R. China.
Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou, 510632, P. R. China.
Adv Healthc Mater. 2024 Dec;13(31):e2402505. doi: 10.1002/adhm.202402505. Epub 2024 Sep 5.
Achieving the clinically staged treatment of osteosarcoma-associated bone defects encounters the multiple challenges of promptly removing postoperative residual tumor cells and bacterial infection, followed by bone reconstruction. Herein, a core/shell hydrogel with multiple-effect combination is designed to first exert antitumor and antibacterial activities and then promote osteogenesis. Specifically, doxorubicin (DOX) is loaded by magnesium-iron-based layered double hydroxide (LDH) to prepare LDOX, which is introduced into a thermo-sensitive hydrogel to serve as an outer shell of the core/shell hydrogel, meanwhile, LDH-contained liquid crystal hydrogel, abbreviated as LCgel-L, is served as an inner core. At the early stage of treatment, the dissociation of the outer shell triggered by moderate hyperthermia led to the thermo-sensitive release of LDOX, which can be targeted for the release of DOX within tumor cells, thereby promptly removing postoperative residual tumor cells based on the synergistic effect of photothermal therapy (PTT) and DOX, and postoperative bacterial infection can also be effectively prevented by PTT simultaneously. More importantly, the dissociation of the outer shell prompted the full exposure of the inner core, which will exert osteogenic activity based on the synergy of liquid crystal hydrogel as well as LDH-induced mild hyperthermia and ion effects, thereby enabling "temporal regulation" treatment of osteosarcoma-associated bone defects. This study provides a valuable insight for the development of osteosarcoma-associated bone repair materials.
实现骨肉瘤相关骨缺损的临床分期治疗面临着多重挑战，即要迅速清除术后残留肿瘤细胞和细菌感染，随后进行骨重建。在此，设计了一种具有多重效应组合的核/壳水凝胶，以首先发挥抗肿瘤和抗菌活性，然后促进骨生成。具体而言，通过镁铁基层状双氢氧化物（LDH）负载阿霉素（DOX）制备LDOX，将其引入热敏水凝胶中作为核/壳水凝胶的外壳，同时，将含LDH的液晶水凝胶（简称为LCgel-L）作为内核。在治疗早期，适度热疗引发外壳解离，导致LDOX热敏释放，其可靶向肿瘤细胞内DOX的释放，从而基于光热疗法（PTT）和DOX的协同作用迅速清除术后残留肿瘤细胞，同时PTT也可有效预防术后细菌感染。更重要的是，外壳解离促使内核完全暴露，其将基于液晶水凝胶以及LDH诱导的温和热疗和离子效应的协同作用发挥成骨活性，从而实现骨肉瘤相关骨缺损的“时间调控”治疗。本研究为骨肉瘤相关骨修复材料的开发提供了有价值的见解。
