PMID- 27918990 OWN - NLM STAT- MEDLINE DCOM- 20170418 LR - 20231112 IS - 1095-7103 (Electronic) IS - 0021-9797 (Print) IS - 0021-9797 (Linking) VI - 490 DP - 2017 Mar 15 TI - Effects of tripolyphosphate on cellular uptake and RNA interference efficiency of chitosan-based nanoparticles in Raw 264.7 macrophages. PG - 520-528 LID - S0021-9797(16)30973-0 [pii] LID - 10.1016/j.jcis.2016.11.088 [doi] AB - Tumor necrosis factor-alpha (TNF-alpha) 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-alpha siRNA (siTNF) to form nanoparticles (NPs). The resultant NPs had a desirable particle size (210-279nm), a slightly positive zeta potential (14-22mV), 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-alpha (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. CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. FAU - Xiao, Bo AU - Xiao B AD - Institute for Clean Energy and Advanced Materials, Faculty of Materials and Energy, Southwest University, Chongqing 400715, PR China; Institute for Biomedical Science, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta 30302, USA. Electronic address: bxiao@gsu.edu. FAU - Ma, Panpan AU - Ma P AD - Institute for Clean Energy and Advanced Materials, Faculty of Materials and Energy, Southwest University, Chongqing 400715, PR China. FAU - Ma, Lijun AU - Ma L AD - Institute for Clean Energy and Advanced Materials, Faculty of Materials and Energy, Southwest University, Chongqing 400715, PR China. FAU - Chen, Qiubing AU - Chen Q AD - Institute for Clean Energy and Advanced Materials, Faculty of Materials and Energy, Southwest University, Chongqing 400715, PR China. FAU - Si, Xiaoying AU - Si X AD - Institute for Clean Energy and Advanced Materials, Faculty of Materials and Energy, Southwest University, Chongqing 400715, PR China. FAU - Walter, Lewins AU - Walter L AD - Institute for Biomedical Science, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta 30302, USA. FAU - Merlin, Didier AU - Merlin D AD - Institute for Biomedical Science, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta 30302, USA; Atlanta Veterans Affairs Medical Center, Decatur 30033, USA. LA - eng GR - I01 BX002526/BX/BLRD VA/United States GR - R01 DK071594/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20161126 PL - United States TA - J Colloid Interface Sci JT - Journal of colloid and interface science JID - 0043125 RN - 0 (N-(2-hydroxypropyl)-3-trimethylammonium chitosan) RN - 0 (Polyphosphates) RN - 0 (Quaternary Ammonium Compounds) RN - 0 (RNA, Small Interfering) RN - 0 (Tumor Necrosis Factor-alpha) RN - 9012-76-4 (Chitosan) RN - NU43IAG5BC (triphosphoric acid) SB - IM MH - Animals MH - Chitosan/*analogs & derivatives/chemistry MH - Macrophages/cytology/*metabolism MH - Mice MH - Nanoparticles/*chemistry MH - Polyphosphates/*chemistry MH - Quaternary Ammonium Compounds/*chemistry MH - RAW 264.7 Cells MH - *RNA Interference MH - RNA, Small Interfering/*administration & dosage/genetics/pharmacokinetics MH - Tumor Necrosis Factor-alpha/*genetics PMC - PMC5222762 MID - NIHMS834085 OTO - NOTNLM OT - Chitosan OT - Macrophage OT - N-(2-hydroxy)propyl-3-trimethyl ammonium chitosan chloride OT - Nanoparticle OT - RNA interference OT - Tripolyphosphate EDAT- 2016/12/06 06:00 MHDA- 2017/04/19 06:00 PMCR- 2018/03/15 CRDT- 2016/12/06 06:00 PHST- 2016/09/19 00:00 [received] PHST- 2016/11/24 00:00 [revised] PHST- 2016/11/25 00:00 [accepted] PHST- 2016/12/06 06:00 [pubmed] PHST- 2017/04/19 06:00 [medline] PHST- 2016/12/06 06:00 [entrez] PHST- 2018/03/15 00:00 [pmc-release] AID - S0021-9797(16)30973-0 [pii] AID - 10.1016/j.jcis.2016.11.088 [doi] PST - ppublish SO - J Colloid Interface Sci. 2017 Mar 15;490:520-528. doi: 10.1016/j.jcis.2016.11.088. Epub 2016 Nov 26.