Fang Huan, Xu Jie, Ma Hailin, Feng Zijiao, Cheng Yuen Yee, Nie Yi, Guan Yanchun, Liu Yaqian, Song Kedong
State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China; Zhengzhou Institute of Emerging Industrial Technology, Zhengzhou 450000, China.
State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China; Zhengzhou Institute of Emerging Industrial Technology, Zhengzhou 450000, China; Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital and Institute, Shenyang 110042, China.
Int J Biol Macromol. 2025 Feb;288:138680. doi: 10.1016/j.ijbiomac.2024.138680. Epub 2024 Dec 11.
The traditional drug efficacy testing often conducted using two-dimensional (2D) cell culture methods, which do not accurately replicate the complexity of the tumor microenvironment. Melanoma in particular, is known for its high incidence, and aggressive nature, highlighting the need for more sophisticated in vitro models that better simulate the tumor's true biological microenvironment drug research and therapy. In this study, we developed quercetin nanoparticles (QueNPs) with enhanced water solubility and promising tumor therapeutic effects. These nanoparticles were formed through the self-assembly of Pluronic F127 (PF127) and quercetin (Que). To better mimic the in vivo tumor environment, we also created a composite scaffold using three-dimensional (3D) printing technology, incorporating a decellularized extracellular matrix (dECM), which closely resembles the native tissue microenvironment. The scaffold also included gelatin methacryloyl (GelMA), which forms a polymeric network via photocrosslinking, and sodium alginate (SA), which enhances structural stability through ion cross-linking with calcium ions. This combination was used to construct a more physiologically relevant 3D melanoma model. The anti-cancer effects of QueNPs were assessed in both 2D and 3D culture systems. The results showed that tumor cells in the 3D model formed cluster and distributed across the scaffold, creating a more realistic tumor microenvironment compared to the 2D system. Cells in the 3D tumor model exhibited significant resistance to QueNPs, with a time dependent response that resulted in a killing rate of over 90 % by day 14. These findings highlight the efficiency of the QueNPs in the 3D melanoma model and emphasize the importance of incorporation 3D printing and nanomedicine for more accurate and effective drug screening.
传统的药物疗效测试通常采用二维（2D）细胞培养方法进行，这种方法无法准确复制肿瘤微环境的复杂性。特别是黑色素瘤，因其高发病率和侵袭性而闻名，这凸显了需要更复杂的体外模型来更好地模拟肿瘤真实的生物微环境以进行药物研究和治疗。在本研究中，我们开发了具有增强水溶性和良好肿瘤治疗效果的槲皮素纳米颗粒（QueNPs）。这些纳米颗粒是通过普朗尼克F127（PF127）和槲皮素（Que）的自组装形成的。为了更好地模拟体内肿瘤环境，我们还使用三维（3D）打印技术创建了一种复合支架，其中包含脱细胞细胞外基质（dECM），它与天然组织微环境非常相似。该支架还包括甲基丙烯酰化明胶（GelMA），其通过光交联形成聚合物网络，以及海藻酸钠（SA），其通过与钙离子的离子交联增强结构稳定性。这种组合被用于构建更具生理相关性的3D黑色素瘤模型。在2D和3D培养系统中评估了QueNPs的抗癌效果。结果表明，与2D系统相比，3D模型中的肿瘤细胞形成簇并分布在支架上，创造了更逼真的肿瘤微环境。3D肿瘤模型中的细胞对QueNPs表现出显著抗性，具有时间依赖性反应，到第14天时杀伤率超过90%。这些发现突出了QueNPs在3D黑色素瘤模型中的有效性，并强调了结合3D打印和纳米医学进行更准确有效药物筛选的重要性。
