功能化金纳米星作为药物载体用于乳腺癌光热和化疗的协同治疗研究

Functionalized Gold Nano-stars as Chemotherapeutic Drugs Vector for Chemo-and Photothermal Synergistic Therapy of Breast Cancer

采用一步合成法将氯金酸(HAuCl_4)与pH=7.4的4-羟乙基哌嗪乙磺酸(HEPES)缓冲溶液合成尺寸约为25 nm的星形金纳米颗粒(金纳米星),其吸收峰位于750 nm。通过Au-S键将16-巯基十六烷基酸(C_(16)H_(32)O_2S)修饰于金纳米星表面,然后负载抗肿瘤药物盐酸阿霉素(DOX),所得材料的吸收峰红移至800 nm,同时在480 nm处出现DOX特征吸收峰。用牛血清白蛋白(BSA)对其进行包覆,以增加其稳定性和生物相容性,材料的吸收峰红移至806 nm,粒径也显著增大,说明BSA被成功包覆于载药纳米材料表面。将上述载药纳米复合材料与乳腺癌细胞(MCF-7)孵育,考察其光热治疗与化疗的协同治疗效果。细胞活力实验结果表明,单纯的激光照射对细胞存活率基本没有影响;加入未负载DOX的金纳米复合物,并经过激光照射后,相对于对照组细胞存活率为85%;只加入同浓度的DOX并经过激光照射后,细胞的相对存活率为70%;加入负载DOX的金纳米复合材料并经过激光照射后,细胞存活率仅为对照组的25%。上述结果表明,所合成的载药纳米复合材料可对乳腺癌进行光热治疗与化疗的协同治疗,提高对乳腺癌的治疗效率。

Gold nano-stars with average size of 25 nm were prepared using a one-step method simply through mixing of HAuCl4 solution with HEPES buffer（ pH 7. 4）. UV-Vis spectroscopy measurement result showed that the absorption peak of the nano-stars was 750 nm. The 16-mercaptohexadecanoic acid（ C16H32O2S） was conjugated to the gold nano-stars through Au-S bond,and then doxorubicin（ DOX） was loaded onto C16H32O2S through hydrophobic interaction. The absorption peak of the nanomaterial was red shifted to 800 nm and a characteristic peak of DOX at 480 nm occurred. Next,bovine serum albumin（ BSA） was coated onto the surface of the nanomaterials to increase their stability and biocompatibility. Accordingly,the absorption peak was red shifted to 806 nm with an increase of the particle size measured by DLS,which indicated that BSA was successfully wrapped onto the drug-loaded nano-stars. The as-synthesized nanocomposites were added into the breast cancer cells（ MCF-7） to explore the effect of chemo-and photothermal synergistic therapy. The cell viability analysis results showed that pure laser irradiation had no significant effects on cell viability.Nanomaterials without loaded DOX only decreased the cell viability by 15%, which indicated the low cytotoxicity of the drug delivery vector. With the addition of above vector with DOX and laser irradiation,the cell survival rate decreased to 25% compared with the negative control,while the survival rate of the cells was kept 70% after being incubated with the same concentration of free DOX and irradiated with same power density of laser. The above results demonstrated that the as-prepared DOX-loaded nano-stars realized chemoand photothermal synergistic therapy of breast cancer（ MCF-7） with an enhanced therapeutic efficiency.