氧化亚铜纳米粒对前列腺癌的治疗作用及相关机制研究
发布时间：2019-04-27 09:26
【摘要】：纳米医学是医学与纳米科学形成的重要交叉学科,对医学和纳米医学的发展都起到了重要的推动作用。纳米药物作为纳米医学的核心研究领域,受到了广泛的关注。纳米药物具有人为可调控尺寸,可通过各种表面修饰、电荷修饰,被动或主动靶向特定器官,在肿瘤治疗中优势十分显著。目前被研制的纳米药物主要集中于纳米载药系统、纳米分子造影剂、无机纳米药物等诸多领域。许多无机纳米药物表现出独特的性质,本身作为肿瘤靶向给药体系的同时,也可以起到肿瘤杀伤的双重作用。然而许多无机纳米药物在表现出重要的应用前景的同时,也有很多不足,其中毒性作用显著、代谢困难是影响无机纳米药物推广应用的瓶颈。寻找既具有良好抗肿瘤作用,且毒性较低、可快速代谢的无机纳米药物显得很有意义。氧化亚铜纳米粒(Cuprous oxide nanoparticles,CONPs)是一种无机纳米药物,本实验室前期的研究发现氧化亚铜纳米粒表现出选择性的肿瘤细胞凋亡诱导作用,可以选择性诱导黑色素瘤细胞发生凋亡,同时氧化亚铜纳米粒表现出极小的肝肾毒性,且可以被小鼠快速代谢,表现出优越的特性。前列腺癌是全球男性生殖系统中最常见的恶性肿瘤,随着雄激素拮抗剂的不断推广使用,绝大多数患者出现雄激素拮抗剂耐受,表现为生化复发,并且逐步发展成为去势抵抗的前列腺癌(Castration-resistant prostate cancer,CRPC)。去势抵抗性前列腺癌治疗虽然方法不断丰富,但是仍然有很多不足,亟待新疗法的开发。本课题基于黑色素瘤与前列腺癌铜代谢的相似性这一生物学基础,利用前列腺癌细胞系以及前列腺癌皮下荷瘤模型,探讨氧化亚铜纳米粒对去势抵抗性前列腺癌的治疗作用,并对氧化亚铜纳米粒的作用机制进行研究,重点关注氧化亚铜纳米粒对前列腺癌细胞干性的影响。研究发现,氧化亚铜纳米粒可以显著诱导前列腺癌细胞凋亡,对正常前列腺上皮细胞的毒性很小,并且对皮下荷瘤动物模型具有显著的治疗作用,表现出对肿瘤细胞选择性凋亡诱导的作用。机制研究方面,发现氧化亚铜纳米粒可以通过抑制Wnt信号通路,起到抑制前列腺癌细胞的作用。本课题为更好的治疗前列腺癌特别是去势抵抗性前列腺癌提供了一条潜在的治疗方法。
[Abstract]:Nano-medicine is an important cross-discipline between medicine and nano-science, and plays an important role in promoting the development of medicine and nano-science. As the core research field of nano-medicine, nano-drugs have been paid more and more attention. Nano-drugs have man-made adjustable size and can be targeted at specific organs by various surface modification, charge modification, passive or active targeting. The advantages of nano-drugs in tumor treatment are significant. At present, nano-drugs are mainly focused on nano-drug loading system, nano-molecular contrast agent, inorganic nano-drug and so on. Many inorganic nanopharmaceuticals exhibit unique properties. As a target drug delivery system, many inorganic nanopharmaceuticals can also play a dual role in tumor killing at the same time. However, many inorganic nano-drugs not only show an important application prospect, but also have a lot of deficiencies. Among them, the toxicity is obvious, and metabolism difficulty is the bottleneck that affects the popularization and application of inorganic nano-drugs. It is of great significance to search for inorganic nanopharmaceuticals with good antitumor activity and low toxicity, which can be metabolized quickly. Cuprous oxide nanoparticles (Cuprous oxide nanoparticles,CONPs) is an inorganic nano-drug. Previous studies in our laboratory found that cuprous oxide nanoparticles showed selective apoptosis-inducing effect on tumor cells. It can selectively induce apoptosis of melanoma cells, and cuprous oxide nanoparticles show minimal liver and kidney toxicity, and can be metabolized rapidly in mice, showing superior characteristics. Prostate cancer is the most common malignant tumor in the male reproductive system. With the increasing use of androgen antagonists, the majority of patients show tolerance of androgen antagonists, showing biochemical recurrence. And gradually developed into castration-resistant prostate cancer (Castration-resistant prostate cancer,CRPC). Although the treatment of castration-resistant prostate cancer continues to be rich, there are still many deficiencies, and it is urgent to develop a new therapy. Based on the similarity of copper metabolism between melanoma and prostate cancer, the therapeutic effect of cuprous oxide nanoparticles on castrated resistant prostate cancer was investigated by using prostate cancer cell line and prostate cancer subcutaneous tumor model. The mechanism of action of cuprous oxide nanoparticles was studied and the effect of cuprous oxide nanoparticles on the dryness of prostate cancer cells was emphasized. It has been found that cuprous oxide nanoparticles can significantly induce apoptosis of prostate cancer cells, have little toxicity to normal prostatic epithelial cells, and have significant therapeutic effects on subcutaneous tumor-bearing animal models. It showed the effect of inducing selective apoptosis of tumor cells. It was found that cuprous oxide nanoparticles could inhibit prostate cancer cells by inhibiting Wnt signaling pathway. This study provides a potential therapeutic method for better treatment of prostate cancer, especially castrated resistant prostate cancer.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.25
本文编号：2466860
[Abstract]:Nano-medicine is an important cross-discipline between medicine and nano-science, and plays an important role in promoting the development of medicine and nano-science. As the core research field of nano-medicine, nano-drugs have been paid more and more attention. Nano-drugs have man-made adjustable size and can be targeted at specific organs by various surface modification, charge modification, passive or active targeting. The advantages of nano-drugs in tumor treatment are significant. At present, nano-drugs are mainly focused on nano-drug loading system, nano-molecular contrast agent, inorganic nano-drug and so on. Many inorganic nanopharmaceuticals exhibit unique properties. As a target drug delivery system, many inorganic nanopharmaceuticals can also play a dual role in tumor killing at the same time. However, many inorganic nano-drugs not only show an important application prospect, but also have a lot of deficiencies. Among them, the toxicity is obvious, and metabolism difficulty is the bottleneck that affects the popularization and application of inorganic nano-drugs. It is of great significance to search for inorganic nanopharmaceuticals with good antitumor activity and low toxicity, which can be metabolized quickly. Cuprous oxide nanoparticles (Cuprous oxide nanoparticles,CONPs) is an inorganic nano-drug. Previous studies in our laboratory found that cuprous oxide nanoparticles showed selective apoptosis-inducing effect on tumor cells. It can selectively induce apoptosis of melanoma cells, and cuprous oxide nanoparticles show minimal liver and kidney toxicity, and can be metabolized rapidly in mice, showing superior characteristics. Prostate cancer is the most common malignant tumor in the male reproductive system. With the increasing use of androgen antagonists, the majority of patients show tolerance of androgen antagonists, showing biochemical recurrence. And gradually developed into castration-resistant prostate cancer (Castration-resistant prostate cancer,CRPC). Although the treatment of castration-resistant prostate cancer continues to be rich, there are still many deficiencies, and it is urgent to develop a new therapy. Based on the similarity of copper metabolism between melanoma and prostate cancer, the therapeutic effect of cuprous oxide nanoparticles on castrated resistant prostate cancer was investigated by using prostate cancer cell line and prostate cancer subcutaneous tumor model. The mechanism of action of cuprous oxide nanoparticles was studied and the effect of cuprous oxide nanoparticles on the dryness of prostate cancer cells was emphasized. It has been found that cuprous oxide nanoparticles can significantly induce apoptosis of prostate cancer cells, have little toxicity to normal prostatic epithelial cells, and have significant therapeutic effects on subcutaneous tumor-bearing animal models. It showed the effect of inducing selective apoptosis of tumor cells. It was found that cuprous oxide nanoparticles could inhibit prostate cancer cells by inhibiting Wnt signaling pathway. This study provides a potential therapeutic method for better treatment of prostate cancer, especially castrated resistant prostate cancer.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.25
【参考文献】
相关期刊论文 前1条
1 王野;杨峰;;纳米氧化亚铜的制备及其应用的研究进展[J];化学世界;2011年09期
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