PMID- 25818429
OWN - NLM
STAT- MEDLINE
DCOM- 20151231
LR  - 20150330
IS  - 1878-5905 (Electronic)
IS  - 0142-9612 (Linking)
VI  - 52
DP  - 2015 Jun
TI  - Effects of mannose density on in vitro and in vivo cellular uptake and RNAi 
      efficiency of polymeric nanoparticles.
PG  - 229-39
LID - S0142-9612(15)00162-3 [pii]
LID - 10.1016/j.biomaterials.2015.02.044 [doi]
AB  - To evaluate the effects of mannose density on in vitro and in vivo cellular 
      uptake and RNA interference (RNAi) efficiency of polymeric nanoparticles (NPs) in 
      macrophages, mannose-modified trimethyl chitosan-cysteine (MTC) conjugates with 
      mannose densities of 4%, 13%, and 21% (MTC-4, MTC-13, and MTC-21) were 
      synthesized. Tumor necrosis factor-alpha (TNF-alpha) siRNA loaded MTC NPs with 
      particle sizes of  approximately 150 nm exhibited desired structural stability and effectively 
      protected siRNA from enzymatic degradation. Generally, cellular uptake and RNAi 
      efficiency were affected by mannose density. As expected, MTC-21 NPs presented 
      the maximum in vitro uptake and RNAi efficacy in Raw 264.7 cells among all NPs 
      tested. However, MTC-4 NPs exhibited the optimal in vivo uptake by peritoneal 
      exudate cell macrophages (PECs). In the inflammation model of acute hepatic 
      injury, orally delivered MTC-4 and MTC-13 NPs worked better in silencing TNF-alpha 
      expression and alleviating liver damage than MTC-21 NPs. As for the ulcerative 
      colitis model, MTC-4 NPs outperformed MTC-13 and MTC-21 NPs with respect to TNF-alpha 
      knockdown and therapeutic efficacy following oral administration. These results 
      highlighted the importance of ligand density in cellular uptake and RNAi 
      efficiency, which could serve as a guideline in the rational design of targeted 
      nanocarriers for anti-inflammation therapy.
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - Chu, Shuang
AU  - Chu S
AD  - State Key Laboratory of Genetic Engineering, Department of Pharmaceutical 
      Sciences, School of Life Sciences, Fudan University, Shanghai 200433, China.
FAU - Tang, Cui
AU  - Tang C
AD  - State Key Laboratory of Genetic Engineering, Department of Pharmaceutical 
      Sciences, School of Life Sciences, Fudan University, Shanghai 200433, China. 
      Electronic address: tangcui@fudan.edu.cn.
FAU - Yin, Chunhua
AU  - Yin C
AD  - State Key Laboratory of Genetic Engineering, Department of Pharmaceutical 
      Sciences, School of Life Sciences, Fudan University, Shanghai 200433, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150227
PL  - Netherlands
TA  - Biomaterials
JT  - Biomaterials
JID - 8100316
RN  - 0 (Drug Carriers)
RN  - 0 (Ligands)
RN  - 0 (Polymers)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9012-76-4 (Chitosan)
RN  - K848JZ4886 (Cysteine)
RN  - PHA4727WTP (Mannose)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Cell Line
MH  - Chitosan/chemistry
MH  - Cysteine/chemistry
MH  - Drug Carriers/chemistry
MH  - Inflammation/metabolism
MH  - Ligands
MH  - Liver/metabolism/pathology
MH  - Macrophages, Peritoneal/*metabolism
MH  - Male
MH  - Mannose/*chemistry
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nanoparticles/*chemistry
MH  - Particle Size
MH  - Polymers/*chemistry
MH  - RAW 264.7 Cells
MH  - *RNA Interference
MH  - RNA, Small Interfering/metabolism
MH  - Tumor Necrosis Factor-alpha/administration & dosage/chemistry
OTO - NOTNLM
OT  - Cellular uptake
OT  - Gene delivery
OT  - Gene silencing
OT  - Mannose density
OT  - Polymeric nanoparticles
EDAT- 2015/03/31 06:00
MHDA- 2016/01/01 06:00
CRDT- 2015/03/31 06:00
PHST- 2014/09/19 00:00 [received]
PHST- 2015/02/05 00:00 [revised]
PHST- 2015/02/06 00:00 [accepted]
PHST- 2015/03/31 06:00 [entrez]
PHST- 2015/03/31 06:00 [pubmed]
PHST- 2016/01/01 06:00 [medline]
AID - S0142-9612(15)00162-3 [pii]
AID - 10.1016/j.biomaterials.2015.02.044 [doi]
PST - ppublish
SO  - Biomaterials. 2015 Jun;52:229-39. doi: 10.1016/j.biomaterials.2015.02.044. Epub 
      2015 Feb 27.