Long Chuan, Peng Han, Yang Wei, Wang Min, Luo Bo, Hao Jie, Dong Yan, Zuo Wenwei
Department of Otolaryngology, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610000, China.
Department of Oncology, Southwest Hospital, Army Medical University, Chongqing 400038, China.
ACS Omega. 2024 Feb 27;9(10):11998-12005. doi: 10.1021/acsomega.3c09751. eCollection 2024 Mar 12.
Chemotherapy is widely recognized as an important approach for the treatment of cholangiocarcinoma. Gemcitabine (GEM) has been considered a first-line drug for treating cholangiocarcinoma due to its ability to effectively inhibit the proliferation, migration, and invasion of liver cancer cells. However, the systemic toxicity, premature degradation, and lack of tumor-targeting properties of GEM limit its application in cholangiocarcinoma chemotherapy. Additionally, precise targeted delivery of GEM is necessary to align with the current concept of precision medicine. In this study, considering the overexpression of hyaluronic acid (HA) receptors (CD44) on cholangiocarcinoma cells, we designed GEM@ZIF-67-HA NPs by loading GEM onto ZIF-67 and modifying its surface with HA. The structure, size, morphology, and elemental composition of GEM@ZIF-67-HA were analyzed using transmission electron microscopy, Fourier transform infrared spectroscopy, ζ-potential, and isothermal adsorption. Cell toxicity experiments demonstrated that GEM@ZIF-67-HA NPs not only reduced cytotoxicity to normal cells but also effectively inhibited the viability of two types of cholangiocarcinoma tumor cells. In a subcutaneous tumor model, GEM@ZIF-67-HA significantly suppressed tumor growth. The tumor-targeting and controllable properties of GEM@ZIF-67-HA NPs hold promise for further development in the strategy of precise targeted therapy for cholangiocarcinoma.
化疗被广泛认为是治疗胆管癌的重要方法。吉西他滨（GEM）因其能够有效抑制肝癌细胞的增殖、迁移和侵袭，而被视为治疗胆管癌的一线药物。然而，吉西他滨的全身毒性、过早降解以及缺乏肿瘤靶向特性限制了其在胆管癌化疗中的应用。此外，吉西他滨的精确靶向递送对于符合当前的精准医学概念是必要的。在本研究中，考虑到胆管癌细胞上透明质酸（HA）受体（CD44）的过表达，我们通过将吉西他滨负载到ZIF-67上并用HA修饰其表面，设计了GEM@ZIF-67-HA纳米颗粒。使用透射电子显微镜、傅里叶变换红外光谱、ζ电位和等温吸附分析了GEM@ZIF-67-HA的结构、大小、形态和元素组成。细胞毒性实验表明，GEM@ZIF-67-HA纳米颗粒不仅降低了对正常细胞的细胞毒性，还有效抑制了两种胆管癌肿瘤细胞的活力。在皮下肿瘤模型中，GEM@ZIF-67-HA显著抑制了肿瘤生长。GEM@ZIF-67-HA纳米颗粒的肿瘤靶向和可控特性为胆管癌精确靶向治疗策略的进一步发展带来了希望。
