Jing Lin, Du Jingguo, Dong Yichao, Li Lili, Tang Zijun, Liu Xu, Zhong Yonglong, Yuan Mingqing
Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, China.
Department of Thoracic Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, Guangxi Zhuang Autonomous Region, China.
Pharm Dev Technol. 2025 Jan;30(1):90-100. doi: 10.1080/10837450.2024.2448619. Epub 2025 Jan 8.
This study aims to develop a dual-ligand-modified targeted drug delivery system by integrating photosensitizers and chemotherapeutic drugs to enhance anti-glioma effects. The system is designed to overcome the blood-brain barrier (BBB) that hinders effective drug delivery, increase drug accumulation in glioma cells, and thereby enhance therapeutic efficacy.
Liposomes were prepared using the film dispersion-ammonium sulfate gradient technique, co-loading the photosensitizer indocyanine green (ICG) and the chemotherapeutic drug mitoxantrone (MTO). The conjugation of BTP-7 and BR2 to the liposome surface was achieved using an organic phase reaction method. The stability, dispersibility, particle size, and potential of the modified liposomes were tested. Their ability to penetrate the BBB and accumulate in glioma was evaluated in BBB models and cellular uptake studies. Additionally, the anti-tumor activity of this combination approach was assessed.
The resulting liposomes demonstrated significant stability and dispersibility, with an average particle size of 142.3 ± 1.8 nm and a potential of -17.6 mV. BBB model and cellular uptake studies indicated that BTP-7/BR2-ICG/MTO-LP could not only penetrate the BBB but also accumulate in glioma, leading to glioma cell necrosis. The anti-tumor activity evaluation showed that this combination approach exhibited a strong tumor-suppressing effect.
The dual-ligand-modified liposomes developed in this study can penetrate the blood-brain barrier and achieve targeted drug delivery in glioma therapy. The combination of BTP-7 and BR2 not only enhances the carrier's penetration ability but also increases intracellular drug accumulation, thereby improving therapeutic efficacy. This novel therapeutic approach, which combines chemotherapy and photothermal response dual-ligand-modified liposomes delivered to the tumor site, demonstrates the potential to reduce drug-related side effects and improve treatment outcomes.
本研究旨在通过整合光敏剂和化疗药物来开发一种双配体修饰的靶向给药系统，以增强抗胶质瘤效果。该系统旨在克服阻碍有效药物递送的血脑屏障（BBB），增加胶质瘤细胞中的药物积累，从而提高治疗效果。
采用薄膜分散-硫酸铵梯度技术制备脂质体，共载光敏剂吲哚菁绿（ICG）和化疗药物米托蒽醌（MTO）。使用有机相反应法实现BTP-7和BR2与脂质体表面的偶联。测试修饰后脂质体的稳定性、分散性、粒径和电位。在血脑屏障模型和细胞摄取研究中评估它们穿透血脑屏障并在胶质瘤中积累的能力。此外，评估这种联合方法的抗肿瘤活性。
所得脂质体表现出显著的稳定性和分散性，平均粒径为142.3±1.8nm，电位为-17.6mV。血脑屏障模型和细胞摄取研究表明，BTP-7/BR2-ICG/MTO-LP不仅可以穿透血脑屏障，还可以在胶质瘤中积累，导致胶质瘤细胞坏死。抗肿瘤活性评估表明，这种联合方法具有很强的肿瘤抑制作用。
本研究开发的双配体修饰脂质体能够穿透血脑屏障，在胶质瘤治疗中实现靶向给药。BTP-7和BR2的联合不仅增强了载体的穿透能力，还增加了细胞内药物积累，从而提高了治疗效果。这种将化疗和光热反应相结合的新型治疗方法，通过双配体修饰脂质体递送至肿瘤部位，显示出减少药物相关副作用并改善治疗结果的潜力。
