【摘要】：納米醫(yī)學是醫(yī)學與納米科學形成的重要交叉學科,對醫(yī)學和納米醫(yī)學的發(fā)展都起到了重要的推動作用。納米藥物作為納米醫(yī)學的核心研究領(lǐng)域,受到了廣泛的關(guān)注。納米藥物具有人為可調(diào)控尺寸,可通過各種表面修飾、電荷修飾,被動或主動靶向特定器官,在腫瘤治療中優(yōu)勢十分顯著。目前被研制的納米藥物主要集中于納米載藥系統(tǒng)、納米分子造影劑、無機納米藥物等諸多領(lǐng)域。許多無機納米藥物表現(xiàn)出獨特的性質(zhì),本身作為腫瘤靶向給藥體系的同時,也可以起到腫瘤殺傷的雙重作用。然而許多無機納米藥物在表現(xiàn)出重要的應用前景的同時,也有很多不足,其中毒性作用顯著、代謝困難是影響無機納米藥物推廣應用的瓶頸。尋找既具有良好抗腫瘤作用,且毒性較低、可快速代謝的無機納米藥物顯得很有意義。氧化亞銅納米粒(Cuprous oxide nanoparticles,CONPs)是一種無機納米藥物,本實驗室前期的研究發(fā)現(xiàn)氧化亞銅納米粒表現(xiàn)出選擇性的腫瘤細胞凋亡誘導作用,可以選擇性誘導黑色素瘤細胞發(fā)生凋亡,同時氧化亞銅納米粒表現(xiàn)出極小的肝腎毒性,且可以被小鼠快速代謝,表現(xiàn)出優(yōu)越的特性。前列腺癌是全球男性生殖系統(tǒng)中最常見的惡性腫瘤,隨著雄激素拮抗劑的不斷推廣使用,絕大多數(shù)患者出現(xiàn)雄激素拮抗劑耐受,表現(xiàn)為生化復發(fā),并且逐步發(fā)展成為去勢抵抗的前列腺癌(Castration-resistant prostate cancer,CRPC)。去勢抵抗性前列腺癌治療雖然方法不斷豐富,但是仍然有很多不足,亟待新療法的開發(fā)。本課題基于黑色素瘤與前列腺癌銅代謝的相似性這一生物學基礎(chǔ),利用前列腺癌細胞系以及前列腺癌皮下荷瘤模型,探討氧化亞銅納米粒對去勢抵抗性前列腺癌的治療作用,并對氧化亞銅納米粒的作用機制進行研究,重點關(guān)注氧化亞銅納米粒對前列腺癌細胞干性的影響。研究發(fā)現(xiàn),氧化亞銅納米�？梢燥@著誘導前列腺癌細胞凋亡,對正常前列腺上皮細胞的毒性很小,并且對皮下荷瘤動物模型具有顯著的治療作用,表現(xiàn)出對腫瘤細胞選擇性凋亡誘導的作用。機制研究方面,發(fā)現(xiàn)氧化亞銅納米�？梢酝ㄟ^抑制Wnt信號通路,起到抑制前列腺癌細胞的作用。本課題為更好的治療前列腺癌特別是去勢抵抗性前列腺癌提供了一條潛在的治療方法。
[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.
【學位授予單位】：第二軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R737.25

【參考文獻】

相關(guān)期刊論文 前1條

1 王野;楊峰;;納米氧化亞銅的制備及其應用的研究進展[J];化學世界;2011年09期

，

本文編號：2466860