Hakeem Abdul, Zhan Guiting, Xu Qingbo, Yong Tuying, Yang Xiangliang, Gan Lu
National Engineering Research Center for Nanomedicine, Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
J Mater Chem B. 2018 Sep 28;6(36):5768-5774. doi: 10.1039/c8tb01572d. Epub 2018 Aug 28.
Layered double hydroxides (LDHs) have attracted particular attention as drug delivery carriers due to their variable chemical composition, excellent biocompatibility, high anion exchange capacity and controlled drug release. However, their anion exchange capability only meets the requirement for encapsulating drugs with negative charge in aqueous media. Encapsulation of drugs with positive charge into LDHs still remains a big challenge. Herein, we report a facile strategy to obtain highly dispersible doxorubicin-loaded MgAl-LDH nanohybrids (DOX@MgAl-LDH). DOX@MgAl-LDH is stable under physiological conditions and releases DOX in response to an acidic tumor microenvironment. Intracellular tracking of DOX@MgAl-LDH confirms that after internalization into cancer cells via macropinocytosis, clathrin- and lipid raft/caveolae-mediated endocytosis, DOX@MgAl-LDH is transported to lysosomes and then releases DOX to the nucleus. Furthermore, DOX@MgAl-LDH exhibits good tumor targeting, enhanced cellular uptake and cytotoxicity against cancer cells compared with free DOX. In vivo anticancer experiments reveal that DOX@MgAl-LDH significantly inhibits tumor growth with decreased DOX-induced cardiotoxicity compared with free DOX. This study may provide a new approach for highly efficient DOX delivery in cancer therapy.
层状双氢氧化物（LDHs）因其可变的化学成分、优异的生物相容性、高阴离子交换容量和可控的药物释放，作为药物递送载体受到了特别关注。然而，它们的阴离子交换能力仅满足在水性介质中包封带负电荷药物的要求。将带正电荷的药物封装到LDHs中仍然是一个巨大的挑战。在此，我们报道了一种简便的策略来获得高度分散的载阿霉素MgAl-LDH纳米杂化物（DOX@MgAl-LDH）。DOX@MgAl-LDH在生理条件下稳定，并在酸性肿瘤微环境中释放阿霉素。对DOX@MgAl-LDH的细胞内追踪证实，通过巨胞饮作用、网格蛋白介导的内吞作用和脂筏/小窝介导的内吞作用内化到癌细胞后，DOX@MgAl-LDH被转运到溶酶体，然后将阿霉素释放到细胞核。此外，与游离阿霉素相比，DOX@MgAl-LDH表现出良好的肿瘤靶向性、增强的细胞摄取和对癌细胞的细胞毒性。体内抗癌实验表明，与游离阿霉素相比，DOX@MgAl-LDH显著抑制肿瘤生长，同时降低了阿霉素诱导的心脏毒性。这项研究可能为癌症治疗中高效递送阿霉素提供一种新方法。
