State Key Laboratory of Fine Chemicals , Dalian University of Technology , Dalian 116024 , China.
ACS Appl Mater Interfaces. 2018 Mar 7;10(9):7832-7840. doi: 10.1021/acsami.7b19281. Epub 2018 Feb 22.
Tumor-targeted drug delivery systems have been increasingly used to improve the therapeutic efficiency of anticancer drugs and reduce their toxic side effects in vivo. Focused on this point, doxorubicin (DOX)-loaded hydroxyapatite (HAP) nanorods consisting of folic acid (FA) modification (DOX@HAP-FA) were developed for efficient antitumor treatment. The DOX-loaded nanorods were synthesized through in situ coprecipitation and hydrothermal method with a DOX template, demonstrating a new procedure for drug loading in HAP materials. DOX could be efficiently released from DOX@HAP-FA within 24 h in weakly acidic buffer solution (pH = 6.0) because of the degradation of HAP nanorods. With endocytosis under the mediation of folate receptors, the nanorods exhibited enhanced cellular uptake and further degraded, and consequently, the proliferation of targeted cells was inhibited. More importantly, in a tumor-bearing mouse model, DOX@HAP-FA treatment demonstrated excellent tumor growth inhibition. In addition, no apparent side effects were observed during the treatment. These results suggested that DOX@HAP-FA may be a promising nanotherapeutic agent for effective cancer treatment in vivo.
肿瘤靶向药物传递系统已被越来越多地用于提高抗癌药物的治疗效果，并降低其体内的毒副作用。基于这一点，开发了载多柔比星（DOX）的羟基磷灰石（HAP）纳米棒，其由叶酸（FA）修饰（DOX@HAP-FA）组成，用于高效的抗肿瘤治疗。通过原位共沉淀和水热法，以 DOX 为模板合成了载 DOX 的纳米棒，为 HAP 材料中的药物负载提供了一种新方法。由于 HAP 纳米棒的降解，DOX@HAP-FA 在弱酸性缓冲溶液（pH = 6.0）中在 24 小时内可有效地释放 DOX。在叶酸受体介导的内吞作用下，纳米棒表现出增强的细胞摄取和进一步的降解，从而抑制了靶向细胞的增殖。更重要的是，在荷瘤小鼠模型中，DOX@HAP-FA 治疗表现出优异的肿瘤生长抑制作用。此外，在治疗过程中未观察到明显的副作用。这些结果表明，DOX@HAP-FA 可能是一种有前途的纳米治疗剂，可用于体内有效的癌症治疗。
