PMID- 30554018
OWN - NLM
STAT- MEDLINE
DCOM- 20190610
LR  - 20190613
IS  - 1873-4367 (Electronic)
IS  - 0927-7765 (Linking)
VI  - 175
DP  - 2019 Mar 1
TI  - Redox-responsive polymer inhibits macrophages uptake for effective intracellular 
      gene delivery and enhanced cancer therapy.
PG  - 392-402
LID - S0927-7765(18)30896-8 [pii]
LID - 10.1016/j.colsurfb.2018.12.016 [doi]
AB  - The development of advanced gene delivery carriers with stimuli-responsive 
      release manner for tumor therapeutics is desirable, since they can exclusively 
      release the therapeutic gene via their structural changes in response to the 
      specific stimuli of the target site. Moreover, interactions between macrophages 
      and drug delivery systems (DDSs) seriously impair the treatment efficiency of 
      DDSs, thus macrophages uptake inhibition would to some extent improve the 
      intracellular uptake of DDSs in tumor cells. Herein, a PEGylated redox-responsive 
      gene delivery system was developed for effective cancer therapy. PEG modified 
      glycolipid-like polymer (P-CSSO) was electrostatic interacted with p53 to form 
      P-CSSO/p53 complexes, which exhibited an enhanced redox sensitivity in that the 
      disulfide bond was degraded and the rate the plasmid released from P-CSSO was 
      2.29-fold that of nonresponsive platform (P-CSO-SA) in 10 mM levels of 
      glutathione (GSH). PEGylation could significantly weaken macrophages uptake, 
      while enhance the accumulation of P-CSSO in tumor cells both in vitro and in 
      vivo. Compared with nonresponsive complexes (P-CSO-SA/p53) (59.2%) and 
      Lipofectamine 2000/p53 complexes (52.0%), the tumor inhibition rate of 
      P-CSSO/p53 complexes (77.1%) significantly increased, which was higher than 
      CSSO/p53 complexes (69.9%). The present study indicates that tumor 
      microenvironment sensitive and macrophages uptake suppressive P-CSSO/p53 is a 
      powerful in vivo gene delivery system for enhanced anticancer therapy.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Wen, Lijuan
AU  - Wen L
AD  - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, 
      Hangzhou, 310058, China.
FAU - Hu, Yingwen
AU  - Hu Y
AD  - Nanotechnology Characterization Laboratory, Cancer Research Technology Program, 
      Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer 
      Research, Frederick, USA.
FAU - Meng, Tingting
AU  - Meng T
AD  - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, 
      Hangzhou, 310058, China.
FAU - Tan, Yanan
AU  - Tan Y
AD  - Ocean College, Zhejiang University, Zheda Road, Zhoushan, 316021, China.
FAU - Zhao, Mengdan
AU  - Zhao M
AD  - Women's Hospital, School of Medicine, Zhejiang University, 2 Xueshi Road, 
      Hangzhou, 310006, China.
FAU - Dai, Suhuan
AU  - Dai S
AD  - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, 
      Hangzhou, 310058, China.
FAU - Yuan, Hong
AU  - Yuan H
AD  - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, 
      Hangzhou, 310058, China.
FAU - Hu, Fuqiang
AU  - Hu F
AD  - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, 
      Hangzhou, 310058, China. Electronic address: hufq@zju.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20181207
PL  - Netherlands
TA  - Colloids Surf B Biointerfaces
JT  - Colloids and surfaces. B, Biointerfaces
JID - 9315133
RN  - 0 (Drug Carriers)
RN  - 0 (Glycolipids)
RN  - 0 (Micelles)
RN  - 0 (Polymers)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 9012-76-4 (Chitosan)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Carcinoma, Hepatocellular/*drug therapy/metabolism/pathology
MH  - Cell Cycle
MH  - Cell Proliferation
MH  - Chitosan/chemistry
MH  - Drug Carriers/*chemistry
MH  - Female
MH  - *Gene Transfer Techniques
MH  - Glutathione/chemistry
MH  - Glycolipids/chemistry
MH  - Humans
MH  - Liver Neoplasms/*drug therapy/metabolism/pathology
MH  - Macrophages/*metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Micelles
MH  - Oxidation-Reduction
MH  - Polymers/*administration & dosage/chemistry
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Protein p53/*administration & dosage/genetics
MH  - Xenograft Model Antitumor Assays
OTO - NOTNLM
OT  - Cancer therapy
OT  - Gene delivery
OT  - Macrophages
OT  - PEGylation
OT  - Redox-responsive
EDAT- 2018/12/17 06:00
MHDA- 2019/06/14 06:00
CRDT- 2018/12/17 06:00
PHST- 2018/09/21 00:00 [received]
PHST- 2018/11/09 00:00 [revised]
PHST- 2018/12/07 00:00 [accepted]
PHST- 2018/12/17 06:00 [pubmed]
PHST- 2019/06/14 06:00 [medline]
PHST- 2018/12/17 06:00 [entrez]
AID - S0927-7765(18)30896-8 [pii]
AID - 10.1016/j.colsurfb.2018.12.016 [doi]
PST - ppublish
SO  - Colloids Surf B Biointerfaces. 2019 Mar 1;175:392-402. doi: 
      10.1016/j.colsurfb.2018.12.016. Epub 2018 Dec 7.