Key Laboratory of Functional Polymer Materials of the Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin, PR China.
Department of Medical Oncology, Tianjin Union Medical Center (Tianjin People's Hospital), Tianjin, PR China.
Nanomedicine. 2019 Jan;15(1):153-163. doi: 10.1016/j.nano.2018.09.012. Epub 2018 Oct 8.
The clinical translation remains a major challenge for platinum drug loaded nanoparticle due to the complexity of composition and preparation. Here we employed only three ingredients to prepare Pt (IV) prodrug-loaded ligand-induced self-assembled nanoparticles (GA-ALG@Pt NPs) via facile one-pot route for liver tumor treatment. GA-ALG@Pt NPs were found equipped with intelligently ligand self-shielded property in which the internal GA could be induced to expose by initial cellular recognition, resulting in strengthened cellular uptake (20%-30%) and prolonged blood circulation time (3.43 times). Appreciable tumor targeting ability (2 times) and especially tumor selectivity (2.5 times) were obtained. Glutathione-triggered release of therapeutic agent generated satisfactory antitumor effect. Bio-safety is also a distinguishing feature of GA-ALG@Pt NPs that greatly relief the nephrotoxicity and systematic toxicity of cisplatin. This conveniently synthesized nanoparticle processes superior targeting capacity and biosecurity, supplying an effective approach to translational cancer therapy in the future.
临床转化仍然是载铂纳米颗粒的主要挑战，因为其组成和制备都很复杂。在这里，我们仅使用三种成分通过简便的一锅法制备了负载 Pt（IV）前药的配体诱导自组装纳米颗粒（GA-ALG@Pt NPs），用于肝癌治疗。GA-ALG@Pt NPs 具有智能配体自屏蔽特性，其中内部 GA 可通过初始细胞识别诱导暴露，从而增强细胞摄取（20%-30%）和延长血液循环时间（3.43 倍）。获得了可察觉的肿瘤靶向能力（2 倍）和特别的肿瘤选择性（2.5 倍）。谷胱甘肽触发的治疗剂释放产生了令人满意的抗肿瘤效果。生物安全性也是 GA-ALG@Pt NPs 的一个显著特点，极大地减轻了顺铂的肾毒性和系统毒性。这种方便合成的纳米颗粒具有优异的靶向能力和生物安全性，为未来的癌症转化治疗提供了一种有效的方法。
