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蛋白脂质体介导的靶向乙酰胆碱酯酶基因传递用于有效的肝癌治疗。

Protein liposomes-mediated targeted acetylcholinesterase gene delivery for effective liver cancer therapy.

机构信息

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, 200032, People's Republic of China.

Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Public Health Clinical Center, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China.

出版信息

J Nanobiotechnology. 2021 Jan 22;19(1):31. doi: 10.1186/s12951-021-00777-9.

Abstract

BACKGROUND

Effective methods to deliver therapeutic genes to solid tumors and improve their bioavailability are the main challenges of current medical research on gene therapy. The development of efficient non-viral gene vector with tumor-targeting has very important application value in the field of cancer therapy. Proteolipid integrated with tumor-targeting potential of functional protein and excellent gene delivery performance has shown potential for targeted gene therapy.

RESULTS

Herein, we prepared transferrin-modified liposomes (Tf-PL) for the targeted delivery of acetylcholinesterase (AChE) therapeutic gene to liver cancer. We found that the derived Tf-PL/AChE liposomes exhibited much higher transfection efficiency than the commercial product Lipo 2000 and shown premium targeting efficacy to liver cancer SMMC-7721 cells in vitro. In vivo, the Tf-PL/AChE could effectively target liver cancer, and significantly inhibit the growth of liver cancer xenografts grafted in nude mice by subcutaneous administration.

CONCLUSIONS

This study proposed a transferrin-modified proteolipid-mediated gene delivery strategy for targeted liver cancer treatment, which has a promising potential for precise personalized cancer therapy.

摘要

背景

将治疗基因递送至实体瘤并提高其生物利用度的有效方法是基因治疗当前医学研究的主要挑战。具有肿瘤靶向性的高效非病毒基因载体的开发在癌症治疗领域具有非常重要的应用价值。与具有肿瘤靶向潜力的功能蛋白整合的蛋白脂复合物,以及优异的基因传递性能,显示出了靶向基因治疗的潜力。

结果

本研究制备了转铁蛋白修饰的脂质体(Tf-PL),用于将乙酰胆碱酯酶(AChE)治疗基因靶向递送至肝癌。我们发现,所得到的 Tf-PL/AChE 脂质体比商业产品 Lipo 2000 具有更高的转染效率,并在体外显示出对肝癌 SMMC-7721 细胞的优异靶向效果。在体内,Tf-PL/AChE 可以有效地靶向肝癌,并通过皮下给药显著抑制裸鼠皮下移植的肝癌异种移植物的生长。

结论

本研究提出了一种转铁蛋白修饰的蛋白脂复合物介导的基因传递策略,用于靶向肝癌治疗,为精准个性化癌症治疗提供了有前景的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c520/7821407/3f71812d07f8/12951_2021_777_Fig1_HTML.jpg

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