Ge Jiahao, Zhang Kangjun, Hu Weijian, Zhou Haihua, Wu Xiaokang
Department of Hepatobiliary Surgery Affiliated Jinhua Center Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China.
J Fluoresc. 2024 Jul 25. doi: 10.1007/s10895-024-03858-8.
Hepatocellular carcinoma (HCC) is a common malignant tumor originating from liver cells, characterized by complex pathogenesis and limited treatment options such as surgery, chemotherapy, and transplantation. Cisplatin, an effective chemotherapeutic agent, disrupts cancer cell DNA but is hindered by side effects and the need for controlled sustained release to optimize efficacy. Metal-organic frameworks (MOFs) have emerged as promising nanocarriers for precise local drug delivery, reducing required doses and mitigating side effects of chemotherapeutic drugs, thus offering a potential avenue for hepatocellular carcinoma (HCC) treatment. In this research, a rectangular channel MOF (Rumgay H, Ferlay J, Martel C, Georges D, Ibrahim AS, Zheng R, Wei W, Lemmens VEPP, Soerjomataram I (2022) Global, regional and national burden of primary liver cancer by subtype. Eur J Cancer 161:108-118) carrier was synthesized using ligand L as the organic linker coordinated with Cu(II) and I(I). The MOF's structure and fluorescence properties were characterized. Additionally, to enhance substrate biocompatibility, composite carrier materials were prepared by incorporating polylactic acid (PLA) with 1, utilized for cisplatin loading. To evaluate the inhibitory effect of PLA-1@cisplatin on HCC, HepG-2 and Huh-7 HCC cell lines were treated with varying concentrations of the drug for 48 h, and their cell viability was assessed. The results demonstrated a significant dose-dependent reduction in cell viability of both HepG-2 and Huh-7 cells. To explore the potential inhibitory mechanism of PLA-1@cisplatin on HCC, the mRNA levels of GADD45A and NACC1 in HepG-2 and Huh-7 cells post-treatment were measured. GADD45A expression, initially low in HCC cells, was significantly upregulated after drug treatment, while NACC1, typically highly expressed in HCC, showed a significant decrease in mRNA levels with increasing concentrations of PLA-1@cisplatin. These findings indicate that PLA-1@cisplatin effectively upregulates GADD45A expression and downregulates NACC1 expression. Overall, the developed cisplatin-loaded nanoparticle system holds promise for HCC treatment by reducing chemotherapy side effects and enhancing drug efficacy.
肝细胞癌（HCC）是一种常见的起源于肝细胞的恶性肿瘤，其发病机制复杂，治疗选择有限，如手术、化疗和移植。顺铂是一种有效的化疗药物，可破坏癌细胞DNA，但受副作用以及需要控制缓释以优化疗效等因素的限制。金属有机框架（MOF）已成为用于精确局部药物递送的有前景的纳米载体，可减少所需剂量并减轻化疗药物的副作用，从而为肝细胞癌（HCC）治疗提供了一条潜在途径。在本研究中，使用配体L作为有机连接体与Cu(II)和I(I)配位合成了一种矩形通道MOF（Rumgay H, Ferlay J, Martel C, Georges D, Ibrahim AS, Zheng R, Wei W, Lemmens VEPP, Soerjomataram I (2022) Global, regional and national burden of primary liver cancer by subtype. Eur J Cancer 161:108 - 118）载体。对该MOF的结构和荧光性质进行了表征。此外，为提高底物生物相容性，通过将聚乳酸（PLA）与1结合制备了复合载体材料，用于负载顺铂。为评估PLA - 1@顺铂对HCC的抑制作用，用不同浓度的该药物处理HepG - 2和Huh - 7 HCC细胞系48小时，并评估其细胞活力。结果表明，HepG - 2和Huh - 7细胞的细胞活力均呈现出显著的剂量依赖性降低。为探究PLA - 1@顺铂对HCC的潜在抑制机制，测量了处理后HepG - 2和Huh - 7细胞中GADD45A和NACC1的mRNA水平。GADD45A在HCC细胞中最初表达较低，药物处理后显著上调，而NACC1在HCC中通常高表达，随着PLA - 1@顺铂浓度增加，其mRNA水平显著降低。这些发现表明PLA - 1@顺铂有效地上调了GADD45A的表达并下调了NACC1的表达。总体而言，所开发的负载顺铂的纳米颗粒系统有望通过减少化疗副作用和提高药物疗效来治疗HCC。
