核分析方法研究纳米颗粒氧化石墨烯载带端粒酶抑制剂的肿瘤抑制及毒性

In recent years, high specificity, highly selective telomerase inhibitors have become the new "target" of the human anticancer drugs, including antisense oligonucleotides or peptide nucleic acid. However, successful antisense oligonucleotides or peptide nucleic acid require a vector that protects them from nuclease degradation and facilitates cellular uptake of DNA into cells with improved transfection efficiency. graphene oxide(GO), a novel class of 2D carbon-based nanomaterial, has recieved more and more attention in rencent years due to its unique electrical, thermal, and mechanical properties. GO offers several distinct advantages over other nonviral vectors. First of all, GO contains many hydroxyl, carboxylic acid and other reactive groups amenable for chemical modifications. Secondly, GO possesses good biocompatibility due to its rich hydrophilic groups. The project will use functionalized GO as a vector, to absorb and delivery telomerase inhibitor antisense oligonucleotide or peptide nucleic into cells, and to protects them from nuclease degradation. Furthermore, we using isotope 14C, 13C to trace and to quantitatively detect functionalized GO vector. We study delivery efficiency of the nanoparticles vector, the effect of telomerase inhibiton and tumor therapy in vitro or in vivo. Above all, to ensure the safe use of the GO as a carrier, we also study toxicity or the safety of the nanoparticles vector in vitro and in vivo. Our research provides the new application of GO as anticancer drugs.

近年来,高特异性、高选择性的端粒酶抑制剂的研究已成为人类抗肿瘤药物研究的新"靶点"，然而，端粒酶抑制剂不容易进入细胞，并容易被核酸酶降解,是目前面临的一大难题。氧化石墨烯纳米颗粒由于独特的表面及电子特性，含有大量官能团，易于被修饰，良好的生物相容性，并容易进入细胞，是一种非常优秀的载体。本项目将氧化石墨烯进行功能化修饰，作为载体，解决端粒酶抑制剂反义核苷酸或肽核酸难以被细胞摄取和易降解的科学难题；利用同位素14C,13C标记技术标记氧化石墨烯，解决生物体系中的定量、示踪检测难题，从而研究氧化石墨烯载带端粒酶抑制剂反义核苷酸或肽核酸转染进细胞，进行肿瘤治疗的效果和特异性；研究其在生物体内的毒性/安全性的初步研究，保证氧化石墨烯作为端粒酶抑制剂载体的安全使用。为新一代的抗肿瘤药物的研究，提供依据，奠定重要基础。

近年来,高特异性、高选择性的端粒酶抑制剂的研究已成为人类抗肿瘤药物研究的新“靶点”，然而，端粒酶抑制剂不容易进入细胞，并容易被核酸酶降解,是目前面临的一大难题。氧化石墨烯纳米颗粒由于独特的表面及电子特性，含有大量官能团，易于被修饰，良好的生物相容性，并容易进入细胞，是一种非常优秀的载体。本项目合成了氧化石墨烯纳米材料，并利用果蝇模型研究了其体内生物安全性研究，发现氧化石墨烯对果蝇基本无毒性。更进一步并对其进行了PEI和PEG表面功能化修饰，通过细胞实验比较，发现PEI修饰的氧化石墨烯更容易载带端粒酶抑制剂进入细胞，并能够抑制肿瘤细胞的端粒酶活性，抑制肿瘤小鼠体内的肿瘤生长。为新一代的抗肿瘤药物的研究，提供依据，奠定重要基础。