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用于通过钙超载和化疗增强抗肿瘤治疗的叶酸修饰智能响应纳米系统

Folate-Modified Smart Responsive Nanosystems for Enhancing Anti-Tumor Therapy Through Calcium Overload and Chemotherapy.

作者信息

Tang Yongcheng, Huang Jingrong, Cui Cheng, Yang Fengyi, Li Kaifu, Gao Benjian, Fu Shaozhi, Yang Xiaoli

机构信息

Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People's Republic of China.

Academician (Expert) Workstation of Sichuan Province, Metabolic Hepatobiliary and Pancreatic Diseases Key Laboratory of Luzhou City, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People's Republic of China.

出版信息

Int J Nanomedicine. 2025 Aug 23;20:10233-10249. doi: 10.2147/IJN.S523621. eCollection 2025.

Abstract

OBJECTIVE

The combination of DOX and 5-Fu is an important chemotherapeutic regimen but lacks targeting to solid tumor sites. Precise drug delivery via folate-modified nanomaterials is an important measure to improve efficacy and reduce toxicity.

METHODS

CaCO nanoparticles served as the carrier for loading DOX and 5-Fu, followed by encapsulation with folic acid-modified polydopamine (PDA) to form a smart dual drug-carrying nanosystem called FA-DCFP. The nanoparticles (NPs) were characterized and the release kinetics and anti-tumor effectiveness of FA-DCFP were studied in vitro and in vivo.

RESULTS

The prepared nanoparticles had an average particle size of 188.79±0.93nm and exhibited pH-sensitive drug release. Cellular experiments demonstrated that the synergistic effect of tumor cell calcium overload and chemotherapy resulted in tumor cell death. Small animal in vivo imaging showed that FA-DCFP was well enriched in the tumour region. In vivo experiments demonstrated that FA-DCFP exhibited significant inhibition of tumour growth, attenuation of toxic side effects, and good biosafety compared to other groups.

CONCLUSION

An intelligent-responsive nano-dual drug delivery system was developed to enhance the therapeutic effectiveness of tumors through calcium overload synergistic chemotherapy, offering a novel approach to tumor treatment.

摘要

目的

多柔比星(DOX)与5-氟尿嘧啶(5-Fu)联合使用是一种重要的化疗方案,但缺乏对实体瘤部位的靶向性。通过叶酸修饰的纳米材料进行精确药物递送是提高疗效和降低毒性的重要措施。

方法

以碳酸钙纳米颗粒为载体负载DOX和5-Fu,然后用叶酸修饰的聚多巴胺(PDA)包裹,形成一种名为FA-DCFP的智能双载药纳米系统。对纳米颗粒进行表征,并在体外和体内研究FA-DCFP的释放动力学和抗肿瘤效果。

结果

制备的纳米颗粒平均粒径为188.79±0.93nm,表现出pH敏感的药物释放特性。细胞实验表明,肿瘤细胞钙超载与化疗的协同作用导致肿瘤细胞死亡。小动物体内成像显示FA-DCFP在肿瘤区域有良好的富集。体内实验表明,与其他组相比,FA-DCFP对肿瘤生长有显著抑制作用,毒性副作用减轻,且具有良好的生物安全性。

结论

开发了一种智能响应性纳米双药递送系统,通过钙超载协同化疗增强肿瘤治疗效果,为肿瘤治疗提供了一种新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9539/12397506/aafab6bb67bc/IJN-20-10233-g0001.jpg

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