Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, Tumor Hospital of Hebei Province, Shijiazhuang, 050011, Hebei Province, People's Republic of China.
Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, Tumor Hospital of Hebei Province, Shijiazhuang, 050011, Hebei Province, People's Republic of China.
Biomed Pharmacother. 2020 May;125:109988. doi: 10.1016/j.biopha.2020.109988. Epub 2020 Feb 12.
Lung cancer remains the leading cause of cancer associated deaths worldwide. Compared with traditional chemotherapy for non-small cell lung cancer (NSCLC), specific targeted therapies are better choices for advanced patients to improve their survival. In this study, we attempted to fabricate Nitroimidazoles (NI) and Hyaluronic acid (HA) co-decorated, cisplatin (DDP) loaded polymeric nanoparticles (PNPs) (NI/HA-DDP-PNPs) and lipid-polymer hybrid nanoparticles (LPNs) (NI/HA-DDP-LPNs) for the facilitated drug delivery at lung tumor regions (hypoxic regions). In vitro cytotoxicity and cellular uptake; In vivo anti-tumor activity and in vivo tissue biodistribution of PNPs and LPNs were evaluated and compared in lung carcinoma cells and xenograft. Hydrodynamic size of NI/HA-DDP-LPNs was 185.6 ± 4.7 nm, which is larger than that of NI/HA-DDP-PNPs (136.7 ± 3.5 nm). The zeta potential of NI/HA-DDP-PNPs (-31.2 ± 2.7 mV) was more negative than NI/HA-DDP-LPNs (-22.3 ± 2.1 mV). The peak plasma concentration (C) achieved from NI/HA-DDP-PNPs and NI/HA-DDP-LPNs was 35.2 ± 1.6 and 37.3 ± 1.7 μg/mL. The half-life (T) of NI/HA-DDP-PNPs and NI/HA-DDP-LPNs was 12.03 ± 0.75 and 11.78 ± 0.89 h. Area Under Curve (AUC) of NI/HA-DDP-PNPs and NI/HA-DDP-LPNs showed no significant difference while greater than other groups. NI/HA-DDP-LPNs exhibited excellent antitumor effect against drug-resistant human lung cancer A549/DDP cells in vitro and in vivo, better than that of NI/HA-DDP-PNPs. Considering that the low toxicity of NI/HA-DDP-LPNs and NI/HA-DDP-PNPs, NI/HA-DDP-LPNs could be a more promising system for lung cancer targeted therapy.
肺癌仍然是全球癌症相关死亡的主要原因。与传统的非小细胞肺癌（NSCLC）化疗相比，针对晚期患者的特定靶向治疗是改善其生存的更好选择。在这项研究中，我们试图制备硝基咪唑（NI）和透明质酸（HA）共修饰的顺铂（DDP）负载聚合物纳米颗粒（PNPs）（NI/HA-DDP-PNPs）和脂质-聚合物杂化纳米颗粒（LPNs）（NI/HA-DDP-LPNs），以促进药物在肺肿瘤部位（缺氧部位）的递送。在肺癌细胞和异种移植中评估和比较了 PNPs 和 LPNs 的体外细胞毒性和细胞摄取；体内抗肿瘤活性和体内组织分布。NI/HA-DDP-LPNs 的水动力学粒径为 185.6±4.7nm，大于 NI/HA-DDP-PNPs（136.7±3.5nm）。NI/HA-DDP-PNPs 的 zeta 电位（-31.2±2.7mV）比 NI/HA-DDP-LPNs（-22.3±2.1mV）更负。NI/HA-DDP-PNPs 和 NI/HA-DDP-LPNs 的最大血浆浓度（C）分别为 35.2±1.6μg/ml 和 37.3±1.7μg/ml。NI/HA-DDP-PNPs 和 NI/HA-DDP-LPNs 的半衰期（T）分别为 12.03±0.75h 和 11.78±0.89h。NI/HA-DDP-PNPs 和 NI/HA-DDP-LPNs 的曲线下面积（AUC）没有显著差异，但均大于其他组。NI/HA-DDP-LPNs 对体外和体内耐药人肺癌 A549/DDP 细胞表现出优异的抗肿瘤作用，优于 NI/HA-DDP-PNPs。鉴于 NI/HA-DDP-LPNs 和 NI/HA-DDP-PNPs 的低毒性，NI/HA-DDP-LPNs 可能是一种更有前途的肺癌靶向治疗系统。
