Wang Zhenggang, He Zhiyi, Wan Junlai, Chen Anmin, Cheng Peng, Zhu Wentao
Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China.
J Nanobiotechnology. 2024 Mar 3;22(1):89. doi: 10.1186/s12951-024-02372-0.
Despite advances in surgery and chemotherapy, the survival of patients with osteosarcoma (OS) has not been fundamentally improved over the last two decades. Microvesicles (MVs) have a high cargo-loading capacity and are emerging as a promising drug delivery nanoplatform. The aim of this study was to develop MVs as specifically designed vehicles to enable OS-specific targeting and efficient treatment of OS. Herein, we designed and constructed a nanoplatform (YSA-SPION-MV/MTX) consisting of methotrexate (MTX)-loaded MVs coated with surface-carboxyl Fe3O4 superparamagnetic nanoparticles (SPIONs) conjugated with ephrin alpha 2 (EphA2)-targeted peptides (YSAYPDSVPMMS, YSA). YSA-SPION-MV/MTX showed an effective targeting effect on OS cells, which was depended on the binding of the YSA peptide to EphA2. In the orthotopic OS mouse model, YSA-SPION-MV/MTX effectively delivered drugs to tumor sites with specific targeting, resulting in superior anti-tumor activity compared to MTX or MV/MTX. And YSA-SPION-MV/MTX also reduced the side effects of high-dose MTX. Taken together, this strategy opens up a new avenue for OS therapy. And we expect this MV-based therapy to serve as a promising platform for the next generation of precision cancer nanomedicines.
尽管在手术和化疗方面取得了进展，但在过去二十年中骨肉瘤（OS）患者的生存率并未得到根本性改善。微泡（MVs）具有高载药量能力，正成为一种有前景的药物递送纳米平台。本研究的目的是开发MVs作为专门设计的载体，以实现OS特异性靶向和OS的有效治疗。在此，我们设计并构建了一种纳米平台（YSA-SPION-MV/MTX），其由负载甲氨蝶呤（MTX）的MVs组成，表面包覆有与靶向ephrinα2（EphA2）的肽（YSAYPDSVPMMS，YSA）偶联的表面羧基Fe3O4超顺磁性纳米颗粒（SPIONs）。YSA-SPION-MV/MTX对OS细胞显示出有效的靶向作用，这取决于YSA肽与EphA2的结合。在原位OS小鼠模型中，YSA-SPION-MV/MTX通过特异性靶向有效地将药物递送至肿瘤部位，与MTX或MV/MTX相比，具有更强的抗肿瘤活性。并且YSA-SPION-MV/MTX还降低了高剂量MTX的副作用。综上所述，该策略为OS治疗开辟了一条新途径。我们期望这种基于MV的治疗方法能够成为下一代精准癌症纳米药物的有前景的平台。
