通过靶向 CD44 的纳米载体共递送紫杉醇和吉西他滨作为前药，对人胆管癌具有协同抗肿瘤活性。
Co-delivery of paclitaxel and gemcitabine via CD44-targeting nanocarriers as a prodrug with synergistic antitumor activity against human biliary cancer.
机构信息
Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 120-749, South Korea; Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, South Korea.
Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 120-749, South Korea.
出版信息
Biomaterials. 2015;53:763-74. doi: 10.1016/j.biomaterials.2015.03.006. Epub 2015 Mar 30.
Multi-drug delivery focuses on different signaling pathways in cancer cells that have synergistic anti-proliferative effects. In this study, we developed multi-prodrug nanocarriers (MPDNCs) consisting of poly (l-lysine)-carboxylate PTX (PLL-PTX) and hyaluronic acid-conjugated GEM (HA-GEM) for CD44-targeted synergistic biliary cancer therapy. An in vitro study of cell viability and mRNA expression levels and an in vivo study showed that MPDNCs more effectively inhibit proliferation in CD44-overexpressing cancer cells (HuCCT1) than in cells with lower CD44 expression (SCK) by synergistically inducing apoptosis. Consequently, these results demonstrate that MPDNCs are prodrugs with synergistic cancer therapeutic efficacy and effective cellular uptake at target cells compared to free drugs, indicating their strong potential as efficient multi-drug-carrying nano-platforms for cancer treatment.
多药递送系统侧重于癌细胞中具有协同抗增殖作用的不同信号通路。在这项研究中，我们开发了由聚（L-赖氨酸）-羧酸紫杉醇（PLL-PTX）和透明质酸偶联吉西他滨（HA-GEM）组成的多前药纳米载体（MPDNC），用于针对 CD44 的协同胆道癌治疗。细胞活力和 mRNA 表达水平的体外研究以及体内研究表明，MPDNC 通过协同诱导细胞凋亡，比 CD44 表达较低的细胞（SCK）更有效地抑制 CD44 过表达的癌细胞（HuCCT1）的增殖。因此，这些结果表明，与游离药物相比，MPDNC 是具有协同癌症治疗功效的前药，并且能够有效摄取靶细胞，这表明它们作为有效的多药物载纳米平台在癌症治疗方面具有很大的潜力。
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