Kang Yao, Sun Wen, Li Shuyi, Li Mingle, Fan Jiangli, Du Jianjun, Liang Xing-Jie, Peng Xiaojun
State Key Laboratory of Fine Chemicals Dalian University of Technology Dalian 116024 China.
Research Institute of Dalian University of Technology in Shenzhen Gaoxin South fourth Road, Nanshan District Shenzhen 518057 China.
Adv Sci (Weinh). 2019 Apr 30;6(13):1900716. doi: 10.1002/advs.201900716. eCollection 2019 Jul 3.
Targeted drug delivery systems (TDDSs) provide a promising approach to overcome the side effect of traditional chemotherapy by specific tumor targeting and drug release. Hyaluronan (HA), as a selective CD44 targeting group, has been widely used in TDDSs for chemotherapy. However, different molecular weight HAs would demonstrate different binding ability to CD44, which may result in different therapeutic effects. Herein, a silica/hydroxyapatite (MSNs/HAP) hybrid carrier loaded with anticancer drug doxorubicin (DOX) (DOX@MSNs/HAP) is fabricated. HA and oligo HA (oHA) are coated onto the nanoparticles (HA-DOX@MSNs/HAP, oHA-DOX@MSNs/HAP), respectively, to investigate their performance in tumor targeting ability. oHA-DOX@MSNs/HAP shows much higher efficiency cellular uptake and drug release in tumor regions due to more effective CD44 targeting of oHA. Thus, the anticancer effect of oHA-DOX@MSNs/HAP is significantly enhanced compared to HA-DOX@MSNs/HAP, as demonstrated in a tumor-bearing mouse model. This study may enable the rational design of nanodrug systems for future tumor-targeted chemotherapy.
靶向给药系统（TDDSs）为通过特异性肿瘤靶向和药物释放克服传统化疗的副作用提供了一种有前景的方法。透明质酸（HA）作为一种选择性靶向CD44的基团，已广泛应用于化疗的TDDSs中。然而，不同分子量的HA对CD44的结合能力不同，这可能导致不同的治疗效果。在此，制备了负载抗癌药物阿霉素（DOX）的二氧化硅/羟基磷灰石（MSNs/HAP）混合载体（DOX@MSNs/HAP）。分别将HA和低聚HA（oHA）包覆在纳米颗粒上（HA-DOX@MSNs/HAP、oHA-DOX@MSNs/HAP），以研究它们在肿瘤靶向能力方面的性能。由于oHA对CD44的靶向作用更有效，oHA-DOX@MSNs/HAP在肿瘤区域表现出更高的细胞摄取效率和药物释放。因此，如在荷瘤小鼠模型中所示，与HA-DOX@MSNs/HAP相比，oHA-DOX@MSNs/HAP的抗癌效果显著增强。这项研究可能有助于为未来的肿瘤靶向化疗合理设计纳米药物系统。
