Effects of tripolyphosphate on cellular uptake and RNA interference efficiency of chitosan-based nanoparticles in Raw 264.7 macrophages

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• 作者：Bo Xiao^a ; ^b ; ^{bxiao@gsu.edu} ; Panpan Ma^a ; Lijun Ma^a ; Qiubing Chen^a ; Xiaoying Si^a ; Lewins Walter^b ; Didier Merlin^b ; ^c
• 关键词：Chitosan ; N-(2-hydroxy)propyl-3-trimethyl ammonium chitosan chloride ; Tripolyphosphate ; Nanoparticle ; RNA interference ; Macrophage
• 刊名：Journal of Colloid and Interface Science
• 出版年：2017
• 出版时间：15 March 2017
• 年：2017
• 卷：490
• 期：Complete
• 页码：520-528
• 全文大小：1857 K
• 卷排序：490

文摘

Tumor necrosis factor-α (TNF-α) is a major pro-inflammatory cytokine that is mainly secreted by macrophages during inflammation. Here, we synthesized a series of N-(2-hydroxy)propyl-3-trimethyl ammonium chitosan chlorides (HTCCs), and then used a complex coacervation technique or tripolyphosphate (TPP)-assisted ionotropic gelation strategy to complex the HTCCs with TNF-α siRNA (siTNF) to form nanoparticles (NPs). The resultant NPs had a desirable particle size (210–279 nm), a slightly positive zeta potential (14–22 mV), and negligible cytotoxicity against Raw 264.7 macrophages and colon-26 cells. Subsequent cellular uptake tests demonstrated that the introduction of TPP to the NPs markedly increased their cellular uptake efficiency (to nearly 100%) compared with TPP-free NPs, and yielded a correspondingly higher intracellular concentration of siRNA. Critically, in vitro gene silencing experiments revealed that all of the TPP-containing NPs showed excellent efficiency in inhibiting the mRNA expression level of TNF-α (by approximately 85–92%, which was much higher than that obtained using Oligofectamine/siTNF complexes). Collectively, these results obviously suggest that our non-toxic TPP-containing chitosan-based NPs can be exploited as efficient siTNF carriers for the treatment of inflammatory diseases.