Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197, Rui Jin Er Road, Shanghai 200025, China and Institute of Biomedical Sciences, Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China.
Institute of Biomedical Sciences, Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China.
J Mater Chem B. 2020 Mar 25;8(12):2410-2417. doi: 10.1039/d0tb00017e.
Gemcitabine (GEM) has been the recommended first-line drug for patients with pancreatic ductal adenocarcinoma cancer (PDAC) for the last twenty years. However, GEM-based treatment has failed in many patients because of the drug resistance acquired during tumorigenesis and development. To override resistance to GEM in pancreatic cancer, we developed a visualisable, photothermally controlled, drug release nanosystem (VPNS). This nanosystem has NaLuF4:Nd@NaLuF4 nanoparticles as the luminescent core, octabutoxyphthalocyanine palladium(ii) (PdPc) as the photothermal agent, and phosphorylated gemcitabine (pGEM) as the chemodrug. pGEM, one of the active forms of GEM, can circumvent the insufficient activation of GEM in cancer cell metabolism. The NaLuF4:Nd@NaLuF4 nanoparticles were employed to visualise the tumor lesion in vivo by their near-infrared luminescence. The near-infrared light-triggered photothermal effect from PdPc could trigger the release of pGEM loaded in a thermally responsive ligand and simultaneously enable photothermal cancer treatment. This work presents an effective method that suppresses the growth of tumour cells with dual-mode treatment and enables the improved treatment of orthotopic nude mice afflicted with pancreatic cancer.
吉西他滨 (GEM) 作为一线药物已被推荐用于治疗胰腺导管腺癌 (PDAC) 患者近 20 年。然而，由于肿瘤发生和发展过程中获得的药物耐药性，基于 GEM 的治疗在许多患者中失败。为了克服胰腺癌对 GEM 的耐药性，我们开发了一种可视化、光热控制、药物释放纳米系统 (VPNS)。该纳米系统以 NaLuF4:Nd@NaLuF4 纳米颗粒作为发光核心，以八丁氧基酞菁钯(ii) (PdPc) 作为光热剂，以磷酸化吉西他滨 (pGEM) 作为化疗药物。pGEM 是 GEM 的一种活性形式，可避免 GEM 在癌细胞代谢中激活不足。NaLuF4:Nd@NaLuF4 纳米颗粒通过近红外发光在体内可视化肿瘤病变。PdPc 的近红外光触发光热效应可以触发负载在热响应配体中的 pGEM 的释放，同时实现光热癌症治疗。这项工作提出了一种有效的方法，通过双重模式治疗抑制肿瘤细胞的生长，并改善原位裸鼠胰腺癌的治疗效果。
