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树状聚合物介导的针对 polo 样激酶的 siRNA 靶向治疗三阴性乳腺癌。

Dendrimer mediated targeting of siRNA against polo-like kinase for the treatment of triple negative breast cancer.

机构信息

Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad, India.

Laboratoire de Chimie de Coordination du CNRS (LCC), Toulouse, France.

出版信息

J Biomed Mater Res A. 2019 Sep;107(9):1933-1944. doi: 10.1002/jbm.a.36701. Epub 2019 Apr 29.


DOI:10.1002/jbm.a.36701
PMID:31008565
Abstract

Irresponsiveness of triple negative breast cancer (TNBC) toward conventional therapies has drawn attention toward siRNA therapeutics. In gene delivery, dendrimers are gaining significant attention due to their characteristic features and polo-like kinase (PLK1) is reported as a potential target for TNBC. In this work, phosphorus and polyamidoamine dendrimer (generation 3 and 4 of each type) are explored to address delivery challenges of PLK1 siRNA (siPLK1). Dendriplexes were formed and complexation was found at 3:1 N/P ratio for all dendrimers by gel electrophoresis. Complexation was also supported by zeta potential, circular dichroism and intercalation assay. Dendriplexes were found to be stable in presence of ribonuclease and serum. Dendriplexes resulted in enhanced cell uptake of siPLK1 compared to siPLK1 solution in MDA-MB-231 and MCF-7 cells. Dendriplexes caused increased cell arrest in sub-G1 phase compared to solution. These observations suggested phosphorus and polyamidoamine dendrimers as potential carriers for siPLK1 delivery to treat TNBC.

摘要

三阴性乳腺癌(TNBC)对常规疗法的不响应引起了人们对 siRNA 治疗的关注。在基因传递中,由于树状聚合物具有特征性,因此引起了人们的关注,并且有报道称丝氨酸/苏氨酸激酶(PLK1)是 TNBC 的潜在靶标。在这项工作中,探索了磷和聚酰胺胺树状聚合物(每种类型的第 3 代和第 4 代),以解决 PLK1 siRNA(siPLK1)的传递挑战。通过凝胶电泳发现,所有树状聚合物在 3:1 的 N/P 比下形成了树状聚合物,并发生了复合物形成。通过 zeta 电位、圆二色性和嵌入测定也支持了复合物的形成。在存在核糖核酸酶和血清的情况下,树状聚合物复合物是稳定的。与 siPLK1 溶液相比,树状聚合物复合物使 MDA-MB-231 和 MCF-7 细胞中 siPLK1 的细胞摄取增加。与溶液相比,树状聚合物复合物使细胞在 sub-G1 期的阻滞增加。这些观察结果表明,磷和聚酰胺胺树状聚合物是将 siPLK1 递送至治疗 TNBC 的潜在载体。

相似文献

[1]
Dendrimer mediated targeting of siRNA against polo-like kinase for the treatment of triple negative breast cancer.

J Biomed Mater Res A. 2019-4-29

[2]
Comparison of cationic liposome and PAMAM dendrimer for delivery of anti-Plk1 siRNA in breast cancer treatment.

Pharm Dev Technol. 2019-10-31

[3]
Antibody h-R3-dendrimer mediated siRNA has excellent endosomal escape and tumor targeted delivery ability, and represents efficient siPLK1 silencing and inhibition of cell proliferation, migration and invasion.

Oncotarget. 2016-3-22

[4]
Combination Treatment of Polo-Like Kinase 1 and Tankyrase-1 Inhibitors Enhances Anticancer Effect in Triple-negative Breast Cancer Cells.

Anticancer Res. 2018-3

[5]
Systemic Administration of siRNA with Anti-HB-EGF Antibody-Modified Lipid Nanoparticles for the Treatment of Triple-Negative Breast Cancer.

Mol Pharm. 2018-3-12

[6]
Therapeutic potential of PLK1 inhibition in triple-negative breast cancer.

Lab Invest. 2019-4-17

[7]
A Novel Allosteric Inhibitor Targets PLK1 in Triple Negative Breast Cancer Cells.

Biomolecules. 2022-3-31

[8]
In Vitro and In Vivo Co-delivery of siRNA and Doxorubicin by Folate-PEG-Appended Dendrimer/Glucuronylglucosyl-β-Cyclodextrin Conjugate.

AAPS J. 2019-4-16

[9]
Polo-like kinase 1: a potential therapeutic option in combination with conventional chemotherapy for the management of patients with triple-negative breast cancer.

Cancer Res. 2012-11-9

[10]
Targeted Treatment of Metastatic Breast Cancer by PLK1 siRNA Delivered by an Antioxidant Nanoparticle Platform.

Mol Cancer Ther. 2017-4

引用本文的文献

[1]
Single-cell encoded gene silencing for high-throughput combinatorial siRNA screening.

Nat Commun. 2024-11-19

[2]
Receptor Targeting Using Copolymer-Modified Gold Nanoparticles for pCMV-Luc Gene Delivery to Liver Cancer Cells In Vitro.

Int J Mol Sci. 2024-5-4

[3]
Advances in Doxorubicin-based nano-drug delivery system in triple negative breast cancer.

Front Bioeng Biotechnol. 2023-11-17

[4]
Current perspectives and trends in nanoparticle drug delivery systems in breast cancer: bibliometric analysis and review.

Front Bioeng Biotechnol. 2023-9-12

[5]
A review of nanomaterials from synthetic and natural molecules for prospective breast cancer nanotherapy.

Front Pharmacol. 2023-5-19

[6]
Recent Advances in Targeted Nanocarriers for the Management of Triple Negative Breast Cancer.

Pharmaceutics. 2023-1-11

[7]
Theranostics for Triple-Negative Breast Cancer.

Diagnostics (Basel). 2023-1-11

[8]
Injectable Nano Drug Delivery Systems for the Treatment of Breast Cancer.

Pharmaceutics. 2022-12-13

[9]
Engineered phosphorus dendrimers as powerful non-viral nanoplatforms for gene delivery: a great hope for the future of cancer therapeutics.

Explor Target Antitumor Ther. 2022

[10]
Emergence of Nanotechnology as a Powerful Cavalry against Triple-Negative Breast Cancer (TNBC).

Pharmaceuticals (Basel). 2022-4-27

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