Effective delivery of p65 shRNA by optimized Tween 85-polyethyleneimine conjugate for inhibition of tumor growth and lymphatic metastasis

To maximize the interference efficacy of pGPU6/Neo-p65 shRNA-expressing pDNA (p65 shRNA) and subsequently more effectively inhibit tumor growth and lymphatic metastasis through blocking the nuclear factor-kappa B (NF-κB) signaling pathway, seven Tween 85-polyethyleneimine (PEI) conjugates (TnPs, n=2...

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Bibliographic Details
Published in:Acta biomaterialia 2014-06, Vol.10 (6), p.2674-2683
Main Authors: Xiao, Jisheng, Duan, Xiaopin, Meng, Qingshuo, Yin, Qi, Zhang, Zhiwen, Yu, Haijun, Chen, Lingli, Gu, Wangwen, Li, Yaping
Format: Article
Language:English
Subjects:
Animals
Breast cancer
Cell Line, Tumor
Female
Humans
Lymphatic Metastasis
Mice
Mice, Nude
Nanoparticles
Neoplasms - metabolism
Neoplasms - pathology
p65 shRNA
Polyethyleneimine - chemistry
Polysorbates - chemistry
RNA, Small Interfering - administration & dosage
Tween 85-PEI conjugates
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Summary:To maximize the interference efficacy of pGPU6/Neo-p65 shRNA-expressing pDNA (p65 shRNA) and subsequently more effectively inhibit tumor growth and lymphatic metastasis through blocking the nuclear factor-kappa B (NF-κB) signaling pathway, seven Tween 85-polyethyleneimine (PEI) conjugates (TnPs, n=2, 3, 4, 5, 6, 7 and 8), which differed in the length of the polymethylene [–(CH2)n–] spacer between Tween 85 and PEI, were synthesized and investigated. The results showed that the transfection efficiency and cytotoxicity both increased with the spacer chain length. Then, TnPs with a [–(CH2)6–] spacer (T6P) were chosen to deliver p65 shRNA to a tumor and subsequently inhibit tumor growth and lymphatic metastasis. The T6P/p65 shRNA complex nanoparticles (T6Ns) could significantly down-regulate p65 expression in breast cancer cells, and consequently inhibit cell invasion and disrupt the tube formation. Most importantly, T6Ns accumulated greatly in tumor tissue, and as a result, significantly inhibited the growth and lymphatic metastasis of breast cancer xenograft. All these results indicated that the transfection efficacies of cationic amphiphiles could be significantly modulated by minor structural variations, and that T6P was promising for the effective delivery of p65 shRNA to knock down the expression of the key metastasis-driving genes and inhibit tumor growth and metastasis.
ISSN:1742-7061
1878-7568
DOI:10.1016/j.actbio.2014.02.009