CSP-GNPs对宫颈癌的靶向放疗增敏作用及其机制的研究

Cervical cancer is common malignant tumors in the female. At present,Radiotherapy is a one of main method of the clinical treatment. The targeted radiosensitizer markedly enhances radiosensitization of cancer cells. Its application is an effective way for improved efficacy of Radiotherapy. But, now there were not yet suited sensitizer using to clinic. In our previous work, the specific peptide binding cervical cancer (CSP) first was selected and identified, and the peptide-gold nanoparticles compound (CSP-GNPs) were obtained. In vitro experiments, it was found that CSP-GNPs enhance radiosensitization of cancer cells. In this project, The radiosensitization of CSP-GNPs will be further detected in cervical cancer cell line and nude mice xenograft tumor model of human cervical cancer, and its mechanism will be explored. the targeting effect of CSP-GNPs will be validated by using nude mice xenograft tumor model of human cervical cancer. Pharmacokinetics of CSP-GNPs will be studied in tumor bearing nude mice. The security of CSP-GNPs will be assessed. These will offer a basis for the clinical drug research. This project is expected to find a new targeted radiosensitizer for therapy of cervical cancer, and there were good application prospects. It will provide new methods and effective exploration for treatments of cervical cancer.

宫颈癌是女性常见恶性肿瘤，放疗是治疗宫颈癌的主要方法之一。靶向放射增敏剂将极大地提高肿瘤对放疗的敏感性，是改善放疗疗效的有效途径。但是，尚无理想的靶向放射增敏剂应用于临床。我们前期工作，首次筛选、鉴定出宫颈癌特异性结合肽(cervical cancer specific binding peptide,CSP)，并将其与纳米金（gold nanoparticles,GNPs）相连，观察到这连肽纳米金（CSP-GNPs）能明显地增强癌细胞对放射的敏感性。本项目将建立宫颈癌裸鼠移植瘤模型，验证CSP-GNPs的靶向定位效果；检测CSP-GNPs对宫颈癌细胞株的放疗增敏作用，采用移植瘤模型进行体内放疗增敏实验，并探讨其作用机制；进行CSP-GNPs在荷瘤裸鼠的药代动力学研究，对其安全性进行评估。本项目的实施有望发现新的宫颈癌靶向放射增敏剂，具有很好的应用前景，为宫颈癌治疗提供崭新思路和有益探索。

宫颈癌是女性常见恶性肿瘤，放疗是其治疗的主要方法之一。靶向放射增敏剂将极大地提高肿瘤放疗敏感性，是改善放疗疗效的有效途径。但尚无理想的靶向放疗增敏剂用于临床。.利用体内噬菌体展示技术筛选宫颈癌特异性结合肽（CSPs）并进行验证。结果：1.获得5个重复率较高的短肽GDALFSVPLEVY、TLHQPPSSANWI、FTPGGNTYAGQP、SIDDQRDVAEFA及KQNLAEG，分别命名为CSP-GD、CSP-TL、CSP-FT、CSP-SI、CSP-KQ。2.体内回输所筛选的5种噬菌体单克隆，结果CSP-GD、CSP-FT、CSP-SI及CSP-KQ噬菌体单克隆在体内可特异性靶向宫颈癌裸鼠移植瘤。3.合成5-FITC-CSPs。经FITC-CSP-GD、FITC-CSP-FT、FITC-CSP-SI或FITC-CSP-KQ共孵的宫颈癌细胞有明显绿色荧光，且以细胞膜和细胞质最为明显，但在对照组MGC803细胞中未见绿色荧光；与FITC-NCSPs孵育的细胞中均未见绿色荧光。4.免疫组织荧光染色结果表明，CSP-GD和CSP-KQ分别对人宫颈腺癌和宫颈鳞癌组织有较强的特异性结合能力（P＜0.01）。通过体内外实验筛选获得了4条宫颈癌特异性结合肽，其中2条（CSP-GD和CSP-KQ）对人宫颈癌细胞及宫颈癌组织有很好的特异性结合能力。5.CCK8结果表明CSP-GD、CSP-KQ对SiHa、C-33A细胞均无明显生长抑制作用。.CSPs-AuNPs的制备。结果：成功制备粒径为20 nm的AuNPs，并用CSP-GD修饰获得CSP-GD-AuNPs。将进一步研究CSP-GD-AuNPs对宫颈癌细胞放疗敏感性的影响。.本项目的实施有望发现新的宫颈癌靶向放疗增敏剂，具有很好的应用前景，为宫颈癌治疗提供崭新思路和有益探索。