新型乳腺癌靶向小分子多肽性能初探

Preliminary study on the properties of novel breast cancer targeting small molecular peptides

目的本研究经固相合成法设计并合成一种新的多肽分子(AR),探讨其乳腺癌靶向性及生物安全性。方法以多种乳腺细胞为模型,通过共聚焦和流式试验探究该荧光多肽分子探针的细胞摄取特异性并检测其对细胞周期的影响;通过CCK8法探讨其细胞毒性,明确其生物安全性。结果共聚焦荧光成像和流式细胞分析结果显示MCF-7细胞的荧光强度明显高于正常乳腺上皮细胞MCF-10A以及其它类型乳腺癌细胞,验证了该探针具有良好的MCF-7细胞靶向特异性;CCK8结果显示,不同浓度AR-FITC处理后的MCF-7细胞存活率仍高于80%,表明该多肽探针具有较低的细胞毒性;细胞周期试验结果显示实验组和对照组MCF-7细胞的S期细胞分别为(12.45±0.75)%、(15.35±0.35)%,该细胞占比差异无统计学意义(P>0.05),表明AR对MCF-7细胞周期没有明显的影响。结论该新型多肽分子具有良好的肿瘤细胞靶向性及生物安全性,是一种较有潜力的乳腺癌靶向分子探针。

Objective In this study,a new polypeptide molecule(AR)was designed and synthesized by solid phase synthesis method to investigate its targeting and biological safety for breast cancer.Methods A variety of breast cells were used as models to investigate the cell uptaken specificity of the fluorescent polypeptide molecular probe and the effect on the cell cycles by confocal microscopy and flow cytometry.Cytotoxicity analysis was per⁃formed by CCK8 to confirm the biosafety of the probe.Results The results of fluorescence and flow cytometry showed that the fluorescence intensity of MCF⁃7 cells was significantly higher than that of the breast epithelial cells MCF⁃10A and other types of breast cancer cells,identifying a good targeting specificity and low cytotoxicity of the probe on MCF⁃7 cells.CCK8 results showed that the cell viability of MCF⁃7 cells treated with different concentra⁃tions of AR⁃FITC was still higher than 80%,indicating that a low cytotoxicity of the probe.Cell cycle showed that the S⁃phase cells of MCF⁃7 cells in the experimental group and the control group were 12.45%±0.75%and 15.35%±0.35%,respectively,which was not statistically significant(P>0.05),identifying that AR had no significant effect on the cell cycle of MCF⁃7 cells.Conclusion The novel peptide has good targeting and biosafety,and is a promis⁃ing molecular probe for breast cancer.