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载乳铁蛋白的金纳米笼用于体外前列腺癌细胞的基因递送。

Lactoferrin-Bearing Gold Nanocages for Gene Delivery in Prostate Cancer Cells in vitro.

机构信息

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, G4 0RE, UK.

College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK.

出版信息

Int J Nanomedicine. 2021 Jun 30;16:4391-4407. doi: 10.2147/IJN.S316830. eCollection 2021.

DOI:10.2147/IJN.S316830
PMID:34234433
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8256823/
Abstract

BACKGROUND

Gold nanocages have been widely used as multifunctional platforms for drug and gene delivery, as well as photothermal agents for cancer therapy. However, their potential as gene delivery systems for cancer treatment has been reported in combination with chemotherapeutics and photothermal therapy, but not in isolation so far. The purpose of this work was to investigate whether the conjugation of gold nanocages with the cancer targeting ligand lactoferrin, polyethylene glycol and polyethylenimine could lead to enhanced transfection efficiency on prostate cancer cells in vitro, without assistance of external stimulation.

METHODS

Novel lactoferrin-bearing gold nanocages conjugated to polyethylenimine and polyethylene glycol have been synthesized and characterized. Their transfection efficacy and cytotoxicity were assessed on PC-3 prostate cancer cell line following complexation with a plasmid DNA.

RESULTS

Lactoferrin-bearing gold nanocages, alone or conjugated with polyethylenimine and polyethylene glycol, were able to condense DNA at conjugate:DNA weight ratios 5:1 and higher. Among all gold conjugates, the highest gene expression was obtained following treatment with gold complex conjugated with polyethylenimine and lactoferrin, at weight ratio 40:1, which was 1.71-fold higher than with polyethylenimine. This might be due to the increased DNA cellular uptake observed with this conjugate, by up to 8.65-fold in comparison with naked DNA.

CONCLUSION

Lactoferrin-bearing gold nanocages conjugates are highly promising gene delivery systems to prostate cancer cells.

摘要

背景

金纳米笼已被广泛用作药物和基因传递的多功能平台，以及癌症治疗的光热剂。然而，它们作为癌症治疗的基因传递系统的潜力，迄今为止仅与化学疗法和光热疗法相结合被报道过，而没有单独使用的报道。本研究的目的是探讨金纳米笼与癌症靶向配体乳铁蛋白、聚乙二醇和聚乙烯亚胺偶联是否能导致体外前列腺癌细胞的转染效率提高，而无需外部刺激。

方法

合成并表征了新型的乳铁蛋白负载的金纳米笼，与聚乙烯亚胺和聚乙二醇偶联。在与质粒 DNA 复合后，评估其对 PC-3 前列腺癌细胞系的转染效率和细胞毒性。

结果

乳铁蛋白负载的金纳米笼，单独或与聚乙烯亚胺和聚乙二醇偶联，都能在偶联物：DNA 重量比为 5:1 及更高时使 DNA 凝聚。在所有金缀合物中，与聚乙二醇和乳铁蛋白偶联的金复合物在重量比为 40:1 时，获得了最高的基因表达，比聚乙烯亚胺高 1.71 倍。这可能是由于与这种偶联物相比，观察到细胞内 DNA 摄取增加了 8.65 倍。

结论

乳铁蛋白负载的金纳米笼缀合物是一种很有前途的前列腺癌细胞基因传递系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5566/8256823/ebdb156b9862/IJN-16-4391-g0011.jpg
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