目的 通过制备聚多巴胺的砒霜纳米递药系统（polydopamine-arsenic trioxide nano-drug delivery system，PDA-ATO@ NDDS）来提高砒霜治疗肿瘤的疗效。方法 在碱性条件下制备搭载砒霜的聚多巴胺纳米粒（PDA-ATO@NDDS），利用单因素考察法优化合成条件；通过透射电子显微镜（transmission electron microscope，TEM）、激光粒度仪表征纳米粒大小；采用透析袋法考察其体外释药特性；采用电感耦合等离子发射光谱（inductive coupled plasma emission spectrometer，ICP）测定其包封率与载药量；并对其体内外抗肿瘤效果进行考察。结果 PDA-ATO@NDDS的最佳合成条件为PVP用量0.5 g，MnCl₂与ATO用量比为1∶5，孵育时间4 h；制备的PDA-ATO@NDDS在TEM下外观呈圆形或类圆形，平均粒径为（243.5±3.5）nm，多分散指数（polydispersity index，PDI）为0.229±0.011；包封率和载药量分别为（8.74±0.03）%和（14.21±0.06）%；体外释放度考察显示，砒霜纳米粒具有一定的缓释效果。细胞毒性实验表明，在低浓度下PDA-ATO@NDDS对细胞具有较强毒性（P＜0.01）。体内药效学表明，ATO与PDA-ATO@NDDS对小鼠肿瘤的抑制具有显著性差异（P＜0.05），PDA-ATO@ NDDS具有较好的肿瘤抑制作用。结论 PDA-ATO@NDDS递药系统提高了砒霜治疗肿瘤的疗效，为砒霜新型递药系统的构建及其在肿瘤治疗中的应用提供参考。

Objective To improve the efficacy of arsenic in the treatment of tumors by preparing a polydopamine-arsenic trioxide nano-drug delivery system (PDA-ATO @NDDS). Methods PDA-ATO@NDDS were prepared under alkaline conditions, and the synthesis conditions were optimized by single-factor method; The size of PDA-ATO@NDDS was characterized by transmission electron microscope (TEM) and laser particle size measurement; The in vitro drug release characteristics were investigated by dialysis bag method; the encapsulation rate and drug loading were determined by inductively coupled plasma emission spectrometer (ICP); And the in vitro and in vivo anti-tumor effects were investigated. Results The optimal synthesis conditions of PDA-ATO@NDDS were 0.5 g of PVP, 1:5 of MnCl₂:ATO, and 4 h of incubation time; the prepared PDA-ATO@NDDS had a round or round-like appearance with an average particle size of (243.5 ± 3.5) nm and PDI of 0.229 ± 0.011. The encapsulation rate and drug loading was (8.74 ± 0.03)% and (14.21 ± 0.06)%, respectively; The in vitro release study showed that PDA-ATO@NDDS could delay the release of arsenic. Cytotoxicity experiments showed that PDA-ATO@NDDS had the strongest toxic to cells at low concentrations (P < 0.01). In vivo pharmacodynamics showed PDA-ATO@ NDDS had a better tumor inhibitory effect compared to ATO (P < 0.05). Conclusion The PDA-ATO@NDDS improved the anti-tumor efficacy of arsenic, and provided a reference for the construction of a novel drug delivery system for arsenic and its application in tumor therapy.

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国家自然科学基金青年科学基金项目（82003954）；浙江省自然科学基金资助项目（LY23H280010）；浙江省大学生科技创新活动计划（新苗人才计划）（2023R410040）；2023年浙江中医药大学校级科研项目（2023JKZKTS23）