聚合多巴胺改性紫杉醇纳米粒靶向治疗乳腺癌骨转移

目的 基于多巴胺衍生物的粘附性，构建表面改性的紫杉醇（PTX）纳米粒，连接阿伦磷酸钠（ALN），对构建的新型纳米粒进行表征并考察其对鼠源性乳腺癌4T1细胞的毒性作用。方法 采用溶剂沉淀法制备PTX纳米粒，将纳米粒放置于0.5 mg/mL的盐酸多巴胺Tris缓冲盐溶液中，在表面形成聚合多巴胺（PDA），随后与亲骨性药物ALN结合，得到新型PTX-PEG₅₀₀₀PCL₁₀₀₀-PDA-ALN纳米粒。ZS型电位仪测定纳米粒的粒径、粒度分布和表面电位；透射电镜观察形态；考察其在不同介质中的稳定性、溶血性；考察ALN用量及钙离子存在条件对新型纳米粒吸附羟基磷灰石（Ca₁₀PO₄）₆（OH）₂，HA]的影响；研究其体外抗4T1乳腺癌细胞活性。结果 成功制得PTX-PEG₅₀₀₀PCL₁₀₀₀-PDA-ALN纳米粒，棒状，粒径为（178.5±2.3）nm，分散指数（PDI）值为0.213±0.06，Zeta电位为（20.12±2.45）mV；在5%葡萄糖、0.9%生理盐水、血浆中基本稳定；无溶血现象；随着ALN用量增加，新型纳米粒对HA吸附率增大，可达48.63%，游离钙离子降低其对HA的吸附能力；MTT结果显示，其对4T1乳腺癌细胞发挥显著抑制作用。结论 制备的PTX-PEG₅₀₀₀PCL₁₀₀₀-PDA-ALN纳米粒粒度分布均匀、稳定性良好、不溶血；通过ALN与HA上的钙离子相结合，亲骨性良好；对4T1细胞发挥毒性作用。

Treatment of bone metastasis of breast cancer with polydopamine modified paclitaxel nanoparticles

Objective Based on the adhesion of dopamine derivatives, the surface modified paclitaxel (PTX) nanoparticles were constructed and connected with Allen sodium phosphate (ALN). The new nanoparticles were characterized and the toxic effects on 4T1 cells were observed. Methods PTX nanoparticles were prepared by solvent precipitation method. The nanoparticles were placed in 0.5 mg/mL dopamine hydrochloride Tris buffer salt solution to form polymeric dopamine (PDA) on the surface, and then combined with the pro osseous drug ALN to obtain novel PTX-PEG_{5 000}PCL_{1 000}-PDA-ALN nanoparticles. Dynamic light scattering and transmission electron microscopy were used to investigate the size and morphology of the new nanoparticle. The stability and hemolysis in different medium were studied. Investigated the effect of ALN dosage and calcium ion condition on the adsorption of novel nanoparticles on hydroxyapatite (Ca₁₀PO₄)₆(OH)₂, HA] and studied its antitumor activity on 4T1 breast cancer in vitro. Results Successfully prepared PTX-PEG_{5 000}PCL_{1 000}-PDA-ALN nanoparticles, rod diameter (178.5 ±2.3) nm, Zeta potential (-20.12 ±2.45) mV, basically stable in 5% glucose, 0.9% saline and plasma, and no hemolysis. In vitro experiment results showed that, with the increase of ALN dosage, the adsorption rate of the new nanoparticles on HA increased, up to 48.63%, and the free calcium ions reduced the adsorption capacity; In vitro cytotoxicity assay (MTT) results showed that, PTX-PEG_{5 000}PCL_{1 000}-PDA-ALN nanoparticles had a significant inhibitory effect on 4T1 breast cancer cells. Conclusion The prepared PTX-PEG_{5 000}PCL₁₀₀₀-PDA-ALN nanoparticles have uniform particle size distribution, good stability and did not cause hemolysis; Moreover, they have good affinity to bone through ALN and calcium ions on HA, and play a toxic role in 4T1 cells.