Wu Xin, Tai Zongguang, Zhu Quangang, Fan Wei, Ding Baoyue, Zhang Wei, Zhang Lijuan, Yao Chong, Wang Xiaoyu, Ding Xueying, Li Qin, Li Xiaoyu, Liu Gaolin, Liu Jiyong, Gao Shen
Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China ; Department of Pharmaceutics, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.
Int J Nanomedicine. 2014 Nov 21;9:5431-40. doi: 10.2147/IJN.S71101. eCollection 2014.
Ligand-mediated prostate cancer (PCa)-targeting gene delivery is one of the focuses of research in recent years. Our previous study reported the successful preparation of aptamer-modified nanoparticles (APT-NPs) in our laboratory and demonstrated their PCa-targeting ability in vitro. However, the mechanism underlying this PCa-targeting effect and their anticancer ability in vivo have not yet been elucidated. The objective of this study was to assess the feasibility of using APT-NPs to deliver micro RNA (miRNA) systemically to PCa cells, to testify their tumor-targeting efficiency, and to observe their biodistribution after systemic administration to a xenograft mouse model of PCa. In addition, the effect of APT depletion and endocytosis inhibitors on cellular uptake was also evaluated quantitatively in LNCaP cells to explore the internalization mechanism of APT-NPs. Finally, blood chemistry, and renal and liver function parameters were measured in the xenograft mouse model of PCa to see whether APT-NPs had any demonstrable toxicity in mice in vivo. The results showed that APT-NPs prolonged the survival duration of the PCa tumor-bearing mice as compared with the unmodified NPs. In addition, they had a potential PCa-targeting effect in vivo. In conclusion, this research provides a prototype for the safe and efficient delivery of miRNA expression vectors to PCa cells, which may prove useful for preclinical and clinical studies on the treatment of PCa.
配体介导的前列腺癌（PCa）靶向基因递送是近年来的研究热点之一。我们之前的研究报道了在我们实验室成功制备适配体修饰的纳米颗粒（APT-NPs），并证明了它们在体外的PCa靶向能力。然而，这种PCa靶向效应的潜在机制及其体内抗癌能力尚未阐明。本研究的目的是评估使用APT-NPs将微小RNA（miRNA）全身递送至PCa细胞的可行性，验证其肿瘤靶向效率，并观察其在PCa异种移植小鼠模型全身给药后的生物分布。此外，还在LNCaP细胞中定量评估了APT耗竭和内吞抑制剂对细胞摄取的影响，以探索APT-NPs的内化机制。最后，在PCa异种移植小鼠模型中测量血液化学指标以及肾和肝功能参数，以观察APT-NPs在体内对小鼠是否有任何明显的毒性。结果表明，与未修饰的纳米颗粒相比，APT-NPs延长了荷PCa肿瘤小鼠的生存时间。此外，它们在体内具有潜在的PCa靶向作用。总之，本研究为将miRNA表达载体安全有效地递送至PCa细胞提供了一个原型，这可能对PCa治疗的临床前和临床研究有用。
