荧光可激活型超小粒径金纳米棒分子探针在乳腺癌细胞诊疗一体化中的研究

Activatable ultrasmall gold nanorods for theranostics in breast cancer cells

目的 制备超小粒径金纳米棒（UGNRs）与荧光素相结合的荧光信号可激活诊疗一体化多功能分子探针，并评估其对肿瘤细胞的光热治疗效果。 方法 采用一步法合成UGNRs，使用巯基乙胺对其进行修饰，利用巯基乙胺的—NH2与羧基化荧光素Cy5的—COOH进行酰胺缩合将两者相连，构建荧光信号可激活的超小粒径金纳米棒（AUGNRs）。使用乳腺癌4T1细胞研究其细胞摄取能力和谷胱甘肽介导成像能力，并应用808 nm激发光照射与AUGNRs共培养的4T1细胞，噻唑蓝（MTT）比色法及钙黄绿素-AM/碘化丙啶（Calcein-AM/PI）染色法观察其光热治疗效果。 结果 成功制备了AUGNRs，其可被4T1细胞快速、高效地摄取，并可产生Cy5荧光信号；其与4T1细胞共培养无明显细胞毒性，在808 nm激光照射下可产生明显的光热效果，有效杀死4T1细胞。 结论 AUGNRs具有荧光可激活性，并可产生显著的光热效果有效杀伤肿瘤细胞。

Objective To develop a fluorescence signal activatable multifunctional molecular probe with theranostics function through combining ultrasmall gold nanorods（UGNRs） with fluorescein, and to evaluate its therapeutic effect on photothermal therapy （PTT） in breast cancer cells. Methods The UGNRs were synthesized by the one-pot seedless method, then the functionalized modification of UGNRs were conducted using cysteamine. Finally, the activatable ultrasmall gold nanorods （AUGNRs） were synthesized by amide condensation of —NH2 of cysteamine and —COOH of carboxylated fluorescein Cy5. The cell uptake ability and GSH-mediated imaging ability of AUGNRs were studied using breast cancer 4T1 cells. 4T1 cells co-cultured with AUGNRs were irradiated with 808 nm excitation light, and the PTT effects were assessed by MTT colorimetric staining and calcein-AM/PI staining. Results The AUGNRs were synthesized successfully, which could be uptaken by 4T1 cells quickly and efficiently, and could achieve intracellular glutathione （GSH） triggered fluorescence recovery. No obvious cytotoxicity of AUGNRs to 4T1 cells was observed in the co-cultivation. Moreover, obvious PTT effects could be induced by 808 nm laser, which could effectively kill 4T1 cancer cells. Conclusion The fluorescence signals of AUGNRs can be induced by intracellular GSH, and tumor cell destruction can be achieved by 808 laser-excitated PTT effects.