Study on the prostate cancer-targeting mechanism of aptamer-modified nanoparticles and their potential anticancer effect in vivo.
Study on the prostate cancer-targeting mechanism of aptamer-modified nanoparticles and their potential anticancer effect in vivo.
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适配体修饰纳米粒子的前列腺癌靶向机制及其体内潜在抗癌作用研究
DOI：
10.2147/ijn.s71101
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发表时间：
2014
影响因子：
8
通讯作者：
Gao S
中科院分区：
文献类型：
--
作者：
Wu X;Tai Z;Zhu Q;Fan W;Ding B;Zhang W;Zhang L;Yao C;Wang X;Ding X;Li Q;Li X;Liu G;Liu J;Gao S
配体介导的前列腺癌靶向基因转移是近年来的研究热点之一。我们之前的研究报告了在我们的实验室中成功制备的适配体修饰的纳米颗粒（APT-NPs），并证明了其体外靶向PCa的能力。然而，这种PCA靶向作用的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microRNA（miRNA）系统递送到PCa细胞的可行性，以验证其肿瘤靶向效率，并观察其在异种移植PCa小鼠模型中的全身给药后的生物分布。此外，还在LNCaP细胞中定量评估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的异种移植小鼠模型中测量血液化学以及肾和肝功能参数，以观察APT-NP在小鼠体内是否具有任何可证实的毒性。结果表明，APT-NPs与未经修饰的NPs相比，延长了PCa荷瘤小鼠的生存时间。此外，它们在体内具有潜在的PCA靶向作用。总之，本研究提供了一个原型的安全和有效的交付的miRNA表达载体PCa细胞，这可能会被证明是有用的临床前和临床研究治疗PCa。
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.