College of Pharmaceutical Science, Zhejiang University, Hangzhou, People's Republic of China.
Zhejiang Institute for Food and Drug Control, NMPA Key Laboratory for Testing and Warning of Pharmceutical Microbiology, Key Laboratory of Drug Contacting Materials Quality Control of Zhejiang Province, Hangzhou, People's Republic of China.
AAPS PharmSciTech. 2022 Jun 16;23(6):167. doi: 10.1208/s12249-022-02316-7.
Hypoxia is an important pathological phenomenon, and it can induce many tumor microenvironment changes, such as accumulations of intracellular lactic acid, decrease of tumor microenvironment pH value, and regulate a series of physiological and pathological processes such as adhesion, metastasis, and immune escape. Hypoxic tumor cells act as a key target for treating tumor. In this research, we designed and prepared PEG-nitroimidazole grafts, PEG-NI, and FA-PEG-NI. We first explored their physical and chemical properties to serve as a drug carrier. Then, the hypoxia-sensitive properties such as particle size changes and drug release were investigated. Finally, the tumor targeting ability was studied in vitro and in vivo, and anti-tumor capacity was determined. Both grafts showed excellent property as a nanodrug carrier and showed favorable drug encapsulation ability of sorafenib with the help of the hydrophobic chain of 6-(BOC-amino) hexyl bromide. The micelles responded to the hypoxic tumor environment with chemical and spatial structure changes leading to sensitive and fast drug release. With the modification of folic acid, FA-PEG-NI gained tumor targeting ability in vivo. FA-PEG-NI graft proved a potential targeting drug delivery system in the treatment of hypoxic hepatocellular carcinoma.
缺氧是一种重要的病理现象，它可以诱导许多肿瘤微环境变化，如细胞内乳酸的积累、肿瘤微环境 pH 值的降低，并调节一系列生理和病理过程，如黏附、转移和免疫逃逸。缺氧肿瘤细胞是治疗肿瘤的关键靶点。在这项研究中，我们设计并制备了聚乙二醇-硝基咪唑接枝物 PEG-NI 和 FA-PEG-NI。我们首先探索了它们的物理化学性质，将其作为药物载体。然后，研究了其粒径变化和药物释放等缺氧敏感特性。最后，在体外和体内研究了肿瘤靶向能力，并确定了抗肿瘤能力。这两种接枝物都表现出作为纳米药物载体的优异性能，并在 6-(BOC-氨基)己基溴的疏水链的帮助下表现出良好的索拉非尼包封能力。胶束通过化学和空间结构的变化对缺氧肿瘤环境做出反应，导致敏感和快速的药物释放。通过叶酸的修饰，FA-PEG-NI 获得了体内肿瘤靶向能力。FA-PEG-NI 接枝物证明了在治疗缺氧性肝细胞癌中具有潜在的靶向药物递送系统。
