通过功能化金纳米颗粒对多细胞结直肠癌球体进行主动靶向光动力治疗。
Actively targeted photodynamic therapy in multicellular colorectal cancer spheroids via functionalised gold nanoparticles.
发表日期:2024 Dec
作者:
Nokuphila Winifred Nompumelelo Simelane, Heidi Abrahamse
来源:
Cellular & Molecular Immunology
摘要:
光动力疗法(PDT)具有克服常见结直肠癌(CRC)治疗方法相关局限性的巨大潜力。使用具有靶向部分的纳米粒子 (NP) 的靶向光敏剂 (PS) 递送系统正在不断被设计,旨在增强 CRC PDT 中的 PS 功效。然而,大多数体外 PDT 研究中靶向 PS 递送系统的优化都是在二维 (2D) 单层细胞培养物上进行的。在我们目前的研究中,我们开发了一种用于体外培养的人结直肠三维多细胞球体(3D MCTS)的纳米PS递送系统。制备聚乙二醇化金纳米颗粒 (PEG-AuNP) 并将其附着到 ZnPcS4PS 上,并用特定 CRC 靶向抗鸟苷酸环化酶单克隆抗体 (mAb) 进一步功能化。成功合成了 ZnPcS4-AuNP-Anti-GCC Ab (BNC) 纳米缀合物,并在暴露于激光照射后研究了其光动力效应,并在培养为 3D MCTS 球体的 Caco-2 细胞中证明了增强的抗癌作用。我们的研究结果表明,靶向 BNC 纳米缀合物可以提高 PDT 的疗效,并凸显 3D MCTS 肿瘤模型用于评估靶向 PDT 的潜力。
Photodynamic therapy (PDT) holds great potential to overcome limitations associated with common colorectal cancer (CRC) treatment approaches. Targeted photosensitiser (PS) delivery systems using nanoparticles (NPs) with targeting moieties are continually being designed, which are aimed at enhancing PS efficacy in CRC PDT. However, the optimisation of targeted PS delivery systems in most, in vitro PDT studies has been conducted on two dimensional (2D) monolayers cell cultures. In our present study, we developed a nano PS delivery system for in vitro cultured human colorectal three-dimensional multicellular spheroids (3D MCTS). PEGylated gold nanoparticles (PEG-AuNPs) were prepared and attached to ZnPcS4PS and further functionalised with specific CRC targeting anti-Guanylate Cyclase monoclonal antibodies(mAb). The ZnPcS4-AuNP-Anti-GCC Ab (BNC) nanoconjugates were successfully synthesised and their photodynamic effect investigated following exposure to laser irradiation and demonstrated enhanced anticancer effects in Caco-2 cells cultivated as 3D MCTS spheroids. Our findings suggest that targeted BNC nanoconjugates can improve the efficacy of PDT and highlight the potential of 3D MCTS tumour model for evaluating of targeted PDT.