Zhou Jianxu, Huo Taotao, Miu Junxian, Wang Ziyi, Shan Xiaoyu, Song Jiaqi, Bai Yuquan, Hao Shuichu, Zhang Chun, Liu Shichang, Wang Biao, Li Guanying
Department of Orthopedic Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P. R. China.
Department of Biophysics, School of Basic Medical Sciences, Health Science Centre, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
ACS Appl Mater Interfaces. 2025 Feb 19;17(7):11073-11084. doi: 10.1021/acsami.4c19608. Epub 2025 Feb 5.
The inhibition of residual tumor recurrence while repairing bone defects poses a challenging issue for postoperative osteosarcoma treatment. Here, we develop a self-assembling peptide hydrogel (GelA) for the targeted delivery of cisplatin (CDDP), aiming to integrate postoperative tumor inhibition with bone defect repair. GelA exhibits exceptional biocompatibility, high loading capacity for CDDP, and superior bone adhesion. After in situ injection to bone defects, CDDP-loaded hydrogel GelA-CDDP demonstrates a strong affinity for hydroxyapatite, thereby facilitating optimal bone adhesion and prolonging the retention time of CDDP in a postoperative wound. Furthermore, GelA-CDDP can regulate the distribution and release behavior of CDDP, minimizing off-target effects and optimizing the therapeutic outcomes of chemotherapy and osteogenesis. Finally, in the orthotopic osteosarcoma transplantation model in mice, postoperative treatment with GelA-CDDP significantly inhibits residual osteosarcoma recurrence as well as repair of bone defects through synergistic osteogenesis promotion and osteoclastic inhibition. We believe that this hydrogel-based therapy strategy holds great promise in achieving simultaneous tumor inhibition and bone defect repair for postoperative osteosarcoma treatment.
在修复骨缺损的同时抑制残留肿瘤复发，这对骨肉瘤术后治疗而言是一个具有挑战性的问题。在此，我们开发了一种用于顺铂（CDDP）靶向递送的自组装肽水凝胶（GelA），旨在将术后肿瘤抑制与骨缺损修复相结合。GelA具有出色的生物相容性、对CDDP的高负载能力以及卓越的骨黏附性。原位注射到骨缺损处后，负载CDDP的水凝胶GelA - CDDP对羟基磷灰石表现出强烈的亲和力，从而促进最佳的骨黏附并延长CDDP在术后伤口中的保留时间。此外，GelA - CDDP可以调节CDDP的分布和释放行为，将脱靶效应降至最低，并优化化疗和成骨的治疗效果。最后，在小鼠原位骨肉瘤移植模型中，用GelA - CDDP进行术后治疗可通过协同促进成骨和抑制破骨细胞，显著抑制残留骨肉瘤复发以及修复骨缺损。我们相信，这种基于水凝胶的治疗策略在实现骨肉瘤术后同步肿瘤抑制和骨缺损修复方面具有巨大潜力。
