基于聚多巴胺的羟基喜树碱纳米晶的制备及其抗骨肿瘤作用

Preparation of polydopamine-based hydroxycamptothecin nanocrystals for potential osteosarcoma treatment

目的:制备以阿伦磷酸钠为靶头的聚多巴胺羟基喜树碱纳米晶,并进行体外抗骨肿瘤的研究。方法:采用碱溶酸沉联合高压均质的方法制备羟基喜树碱纳米晶,通过将盐酸多巴胺置于碱性环境中,在纳米晶表面形成聚多巴胺,随后与阿伦磷酸钠结合得到新型阿伦磷酸钠-聚多巴胺-羟基喜树碱纳米晶。采用动态光散射法、透射电镜法考察粒径及形态,高效液相法测定羟基喜树碱含量,并对其不同介质稳定性、体外释放、溶血性、体外抗骨肉瘤活性进行研究。结果:成功制得阿伦磷酸钠-聚多巴胺-羟基喜树碱纳米晶,球形,粒径为(148.7±3.0)nm,Zeta电位为(-19.5±1.45)m V,在5%葡萄糖、血浆中粒径基本稳定。体外缓慢释放,且具有一定的酸敏特性,在96 h累积释放率达90.04%;体外羟基磷灰石实验证明其亲骨性吸附率达48%;体外细胞毒性实验(MTT)结果显示阿伦磷酸钠-聚多巴胺-羟基喜树碱纳米晶对骨肉瘤(U2OSLucte T-on)细胞具有一定的抑制作用。结论:制备的阿伦磷酸钠-聚多巴胺-羟基喜树碱纳米晶粒径较小、稳定性良好、且具有缓释及酸敏特性、提高了羟基喜树碱抗骨肉瘤(U2OS-Lucte T-on)的作用。

Objective： To prepare polydopamine-based hydroxycamptothecin nanocrystals conjugated with alendronate and explore its anti-osteosarcoma activities in vitro. Methods： Hydroxycamptothecin（ HCPT）nanocrystals were prepared by alkali-solution and acid-isolation combined with high pressure homogenization method.Dopamine（ PDA） catechol is oxidized to form polymerized dopamine in a weak alkaline condition,then conjugate alendronate（ ALN） as the target. The particle size and morphology were measured by dynamic light scattering（ DLS） and transmission electron microscope（ TEM）. The stability in biological media,release study,hemolytic activity was also investigated. The in vitro anticancer cytotoxic activity against human osteosarcoma（ U2 OS-Luc te Ton） was evaluated by MTT assay. Results： ALN-PDA-HCPT nanocrystals had a diameter of（ 148. 7 ± 3. 0） nm and a Zeta potential of（-19. 5 ± 1. 45） m V. It was stable in 5% glucose and plasma. ALN-PDA-HCPT nanocrystalsshowed sustained drug release in vitro and had acid sensitivity characteristics,and its cumulative release reached90. 04% within 96 h in PBS（ p H = 5. 4）. The hydroxyapatite experiments showed adsorption rate of nanocrystals reached 48%. In vitro cytotoxicity-test（ MTT method） indicated that ALN-PDA-HCPT nanocrystals had obvious cytotoxicity against U2 OS cells. Conclusion： ALN-PDA-HCPT nanocrystals have small particle size,good stability,acid-sensitive and controlled-release properties,which improve the anti-osteosarcoma effect of HCPT.