PMID- 29641895
OWN - NLM
STAT- MEDLINE
DCOM- 20190710
LR  - 20190710
IS  - 1526-4602 (Electronic)
IS  - 1525-7797 (Linking)
VI  - 19
IP  - 7
DP  - 2018 Jul 9
TI  - Fine Tuning of Core-Shell Structure of Hyaluronic Acid/Cell-Penetrating 
      Peptides/siRNA Nanoparticles for Enhanced Gene Delivery to Macrophages in 
      Antiatherosclerotic Therapy.
PG  - 2944-2956
LID - 10.1021/acs.biomac.8b00501 [doi]
AB  - Hyaluronic-acid (HA)-coated LOX-1-specific siRNA-condensed cell-penetrating 
      peptide (CPP) nanocomplexes (NCs) were developed for targeted gene delivery to 
      macrophages and suppression of lipid accumulation. The HA coating facilitated the 
      accumulation of nanoparticles at leaky endothelium overexpressing CD44 receptors 
      and was further degraded by hyaluronidase (HAase) intraplaques for exposing the 
      naked CPP NCs and achieving the ultimate location into macrophages. The surface 
      coating of HA was verified by the increased particle size, inverted zeta 
      potential, and TEM images. The targeting mechanism was studied on the established 
      injured endothelium-macrophage coculture system, which revealed that modification 
      of higher molecular weight HA and higher HA coating density on NCs, termed as 
      NPs-3, improved the intracellular uptake of nanoparticles by macrophages. 
      Macrophages internalized NCs via caveolae-mediated endocytosis pathway. Moreover, 
      NPs-3 exhibited better cellular drug efficacy in preventing macrophage-derived 
      foam cell formation than other preparations. Compared with NCs, HA decoration 
      showed enhanced atherosclerotic-lesion-targeting efficiency, proven by results 
      from ex vivo imaging. Furthermore, atheroprotective efficacy study in 
      apoE-deficient mice showed that NPs-3 had the best potent efficacy, which was 
      demonstrated by the fewest atherosclerotic lesions sizes and lipid accumulation, 
      the lowest macrophage infiltration, and the lowest expression of monocyte 
      chemoattractant protein-1 (MCP-1), respectively. Collectively, the HA-coated CPP 
      NCs were promising nanocarriers for efficient macrophage-targeted gene delivery 
      and antiatherogenic therapy.
FAU - Zhao, Yi
AU  - Zhao Y
AD  - Department of Pharmaceutics , China Pharmaceutical University , Nanjing 210009 , 
      P. R. China.
FAU - He, Zhiyu
AU  - He Z
AD  - School of Materials Science and Engineering, Key Laboratory for Polymeric 
      Composite and Functional Materials of Ministry of Education , Sun Yat-sen 
      University , Guangzhou 510275 , P. R. China.
AD  - Department of Materials Science and Engineering and Institute for 
      NanoBioTechnology , Johns Hopkins University , Baltimore , Maryland 21218 , 
      United States.
FAU - Gao, Hai
AU  - Gao H
AD  - Department of Pharmaceutics , China Pharmaceutical University , Nanjing 210009 , 
      P. R. China.
FAU - Tang, Haoyu
AU  - Tang H
AD  - Department of Materials Science and Engineering and Institute for 
      NanoBioTechnology , Johns Hopkins University , Baltimore , Maryland 21218 , 
      United States.
FAU - He, Jianhua
AU  - He J
AD  - Department of Pharmaceutics , China Pharmaceutical University , Nanjing 210009 , 
      P. R. China.
FAU - Guo, Qing
AU  - Guo Q
AD  - Department of Pharmaceutics , China Pharmaceutical University , Nanjing 210009 , 
      P. R. China.
FAU - Zhang, Wenli
AU  - Zhang W
AD  - Department of Pharmaceutics , China Pharmaceutical University , Nanjing 210009 , 
      P. R. China.
FAU - Liu, Jianping
AU  - Liu J
AUID- ORCID: 0000-0003-1825-7122
AD  - Department of Pharmaceutics , China Pharmaceutical University , Nanjing 210009 , 
      P. R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180416
PL  - United States
TA  - Biomacromolecules
JT  - Biomacromolecules
JID - 100892849
RN  - 0 (Cell-Penetrating Peptides)
RN  - 9004-61-9 (Hyaluronic Acid)
SB  - IM
EIN - Biomacromolecules. 2018 Aug 13;19(8):3594-3596. PMID: 30058804
MH  - Animals
MH  - Atherosclerosis/*therapy
MH  - Cell-Penetrating Peptides/*chemistry
MH  - Endocytosis
MH  - Human Umbilical Vein Endothelial Cells/drug effects/metabolism
MH  - Humans
MH  - Hyaluronic Acid/*chemistry
MH  - Macrophages/drug effects/*metabolism
MH  - Male
MH  - Mice
MH  - Nanoparticles/adverse effects/*chemistry
MH  - RNAi Therapeutics/*methods
MH  - THP-1 Cells
MH  - Transfection/*methods
EDAT- 2018/04/12 06:00
MHDA- 2019/07/11 06:00
CRDT- 2018/04/12 06:00
PHST- 2018/04/12 06:00 [pubmed]
PHST- 2019/07/11 06:00 [medline]
PHST- 2018/04/12 06:00 [entrez]
AID - 10.1021/acs.biomac.8b00501 [doi]
PST - ppublish
SO  - Biomacromolecules. 2018 Jul 9;19(7):2944-2956. doi: 10.1021/acs.biomac.8b00501. 
      Epub 2018 Apr 16.