Wang Yanping, Qi Peiyan, Shi Shenbao, Pang Cong, Wang Weijie, Fang Dazhao
Department of Neurosurgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu, People's Republic of China.
Guangzhou International Travel Healthcare Center, Guangzhou Customs District P.R.China, Guangzhou, People's Republic of China.
Nanotechnology. 2025 Jan 30;36(12). doi: 10.1088/1361-6528/adacef.
Glioblastoma (GBM) is a malignant tumor with highly heterogeneous and invasive characteristics leading to a poor prognosis. The CD44 molecule, which is highly expressed in GBM, has emerged as a highly sought-after biological marker. Therapeutic strategies targeting the cell membrane protein CD44 have emerged, demonstrating novel therapeutic potential. In this study, we constructed a nanodrug system (HA-Liposome@Dox) based on hyaluronic acid-engineered liposomes delivering adriamycin to target GBM. The system efficiently encapsulated Dox inside the liposomes through a hydrophilic-hydrophobic interaction mechanism, and the resulting HA-Liposome@Dox exhibited excellent loading efficacy, attributed to its uniform particle size distribution and negatively charged surface. Further evaluation revealed that HA-Liposome@Dox possessed excellent stability and safety and could promote the effective uptake of drug particles by CD44-overexpressing tumor cells, thus exerting a more potent cell-killing effect. Notably, in the treatment of GBM, HA-Liposome@Dox demonstrated significantly greater tumor growth inhibition compared to free Dox and prolonged the survival of tumor-bearing mice. Taken together, the present study not only verified the feasibility of HA-Liposome@Dox as an effective therapeutic tool against GBM and other CD44-positively expressing tumors, but also opened a promising new avenue for the clinical treatment of this type of refractory malignancies.
胶质母细胞瘤(GBM)是一种具有高度异质性和侵袭性特征的恶性肿瘤,预后较差。在GBM中高表达的CD44分子已成为备受关注的生物标志物。针对细胞膜蛋白CD44的治疗策略不断涌现,显示出新的治疗潜力。在本研究中,我们构建了一种基于透明质酸修饰脂质体的纳米药物系统(HA-脂质体@阿霉素),用于向GBM递送阿霉素。该系统通过亲水-疏水相互作用机制将阿霉素有效地包裹在脂质体内,所得的HA-脂质体@阿霉素表现出优异的负载效率,这归因于其均匀的粒径分布和带负电荷的表面。进一步评估表明,HA-脂质体@阿霉素具有优异的稳定性和安全性,能够促进CD44过表达的肿瘤细胞对药物颗粒的有效摄取,从而发挥更强的细胞杀伤作用。值得注意的是,在GBM治疗中,HA-脂质体@阿霉素相比于游离阿霉素显示出显著更强的肿瘤生长抑制作用,并延长了荷瘤小鼠的生存期。综上所述,本研究不仅验证了HA-脂质体@阿霉素作为一种针对GBM和其他CD44阳性表达肿瘤的有效治疗工具的可行性,也为这类难治性恶性肿瘤的临床治疗开辟了一条充满希望的新途径。