Department of Musculoskeletal Tumor, Gansu Provincial Hospital, Lanzhou, China.
Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, 53 Zhengzhou Road, Qingdao, 266042, China.
AAPS PharmSciTech. 2024 Nov 26;25(8):272. doi: 10.1208/s12249-024-02992-7.
Osteosarcoma (OS) is one of the most common primary bone sarcoma with high malignant degree and poor prognosis, for which there is an urgent need to develop novel therapeutic approaches. Recent research has revealed that mifamurtide significantly improved the outcome of OS patients when combined with adjuvant chemotherapy drugs including cisplatin (DDP). The present study aimed to construct a drug delivery system co-loading DDP and mifamurtide. Long-circulating targeted liposomes co-loading DDP and mifamurtide were constructed with Soy lecithin (SPC), cholesterol (Chol) and 1,2-distearoylglycero-3-phosphoethanolamine-n-[poly(ethyleneglycol)] (DSPE-PEG), modified with MMP14 targeting peptide BCY-B in the surface of liposomes. In addition to characterization, the cellular uptake, endocytosis pathway and inhibition on cell viability, migration, invasion and cell apoptosis of MG-63 cells were explored. The constructed liposomal delivery possessed the basic characteristics of liposomes and showed high affinity to MG-63 cells, resulting in high uptake efficiency in MG-63 cells. The endocytosis might be involved in multiple pathways including caveolae-mediated endocytosis, clathrin-mediated endocytosis and macropinocytosis, dependently on energy. The constructed long-circulating targeted liposomes co-loading DDP and mifamurtide significantly inhibited the cell viability, migration, invasion and cell apoptosis of MG-63 cells, improving the antitumor effect of DDP and mifamurtide in vitro. The constructed liposomal delivery system is suitable for co-loading DDP and mifamurtide to achieve active tumor targeting, supplying a new strategy for the treatment of OS.
骨肉瘤（OS）是最常见的原发性骨肉瘤之一，恶性程度高，预后差，因此迫切需要开发新的治疗方法。最近的研究表明，米伐木肽与顺铂（DDP）等辅助化疗药物联合使用时，可显著改善 OS 患者的预后。本研究旨在构建一种同时载药顺铂和米伐木肽的药物传递系统。采用大豆卵磷脂（SPC）、胆固醇（Chol）和 1,2-二硬脂酰基-sn-甘油-3-磷酸乙醇胺-N-[聚（乙二醇）]（DSPE-PEG）构建长循环靶向载药脂质体，在脂质体表面修饰 MMP14 靶向肽 BCY-B。除了对其进行表征外，还研究了 MG-63 细胞的细胞摄取、内吞途径以及对细胞活力、迁移、侵袭和细胞凋亡的抑制作用。构建的脂质体递药系统具有脂质体的基本特征，对 MG-63 细胞表现出高亲和力，导致 MG-63 细胞摄取效率高。内吞作用可能涉及多种途径，包括网格蛋白介导的内吞作用、小窝蛋白介导的内吞作用和大胞饮作用，这取决于能量。构建的长循环靶向载药顺铂和米伐木肽脂质体显著抑制了 MG-63 细胞的活力、迁移、侵袭和细胞凋亡，提高了顺铂和米伐木肽在体外的抗肿瘤作用。构建的脂质体递药系统适合同时载药顺铂和米伐木肽，实现主动肿瘤靶向，为 OS 的治疗提供了新策略。
